Optimizing Cancer Care with Non-FDG PET, Dr. Ashwin Singh Parihar (5-19-25)
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Today we are honored to welcome Dr.
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Ashwin Singh PAAR
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for an lecture entitled Optimizing Cancer Care
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with non FDG pet,
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A focus on FDA approved radiopharmaceuticals.
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Dr. PAAR is trained in nuclear medicine from P-G-I-M-E-R,
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chande Garr India with additional clinical training
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and research fellowship at the Mallinckrodt Institute
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of Radiology, Washington University School of Medicine.
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He is an assistant professor of radiology in the division
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of nuclear medicine at Wash U
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and an attending physician at the Barnes Jewish Hospital.
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His broad clinical and research interests include functional
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imaging and theranostics.
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At the end of the lecture, please join Dr.
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Parr in a q and A session
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where he will address questions you
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may have on today's topic.
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Please remember to use the q
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and a feature to submit your questions so we can get to
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as many as we can before our time is up.
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With that, we are ready to begin today's lecture. Dr.
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Parr, please take it from here.
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Good morning. Uh, everyone, or I guess good afternoon
1:20
or good evening, uh, based on where you're joining from, uh,
1:23
it's my pleasure to talk about some of the non FTG, um, pet,
1:28
uh, FD approved radiopharmaceuticals,
1:30
and these are the radiopharmaceuticals
1:31
that we commonly use in our clinic.
1:33
Um, the, this is not an all encompassing list,
1:37
so the learning objectives for this conference are
1:40
to describe some of the common clinical indications
1:42
that we have for FES, um, SSTR and PSMA pet.
1:46
And again, there are additional radiopharmaceuticals in this
1:49
space that are FD approved,
1:50
but we are going to predominantly focus on these
1:52
as they constitute the bulk of our clinical practice outside
1:56
of the outside of FTG pet.
1:58
So we'll talk about their normal
1:59
bio distribution to begin with.
2:01
That's a crucial step for understanding, uh,
2:04
which all sites have that physiologic tracer, um, activity.
2:08
And then that helps us separate the
2:09
pathology from the physiology.
2:11
We'll also talk about interpreting, uh,
2:13
findings across common pathologies
2:15
and the common clinical indications that we encounter.
2:17
And finally, we also talk about, uh, some
2:20
of the common imaging pitfalls that are relevant to each
2:22
of these radiopharmaceuticals.
2:24
So I'll start off with poll, um, just to kind
2:28
of get you all engaged.
2:30
Um, so the first question is, which
2:32
of these radiopharmaceuticals was the first PET imaging
2:36
agent developed for targeting a receptor on the tumor cells?
2:40
And your options are, um, F 18 fluoro, estradiol,
2:45
gallium 68 p, SMA 11, F 18, flu solovine,
2:49
and F 18 labeled fluoro deoxy glucose.
2:53
And we'll pause for about, um, 20 to 30 seconds just to kind
2:57
of let you all have a look at the question,
3:00
figure out the options.
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And again, the question is the first pet imaging agent, uh,
3:05
which was developed for targeting a receptor, um,
3:08
on the tumor cells.
3:15
Okay, so we have a lot of good responses
3:18
that's quite an engaged audience.
3:20
Um, the majority, I guess, voted for FTG,
3:24
so the answers went away pretty soon,
3:26
but I think I saw FT G was the top contender followed
3:30
by Fluor estradiol.
3:32
Now the answer is Fluor estradiol.
3:34
And, uh, we'll take a look at why.
3:36
First of all, the top two, let me put my pointer on.
3:42
So the top two options, fluoro, estradiol, or FES
3:45
and PSMA are both receptor targeting PET agents used in
3:49
oncology indications for breast cancer, predominantly
3:51
for breast cancer and, um, for prostate cancer.
3:54
Chlorine is also used in prostate cancer,
3:56
but it's not a receptor targeting radiopharmaceutical.
3:59
It, uh, it tracks the amino acid metabolism in the cell in
4:03
the tumor cells and fluoro deoxy glucose tracks the
4:06
glycolysis in happening in the cells.
4:07
So both of these are not receptor
4:09
targeting radiopharmaceuticals.
4:13
So that kind of gave us a nice segue to talk about FES.
4:16
Um, just to kind of give you an idea about the background
4:19
of FES development.
4:21
So FES of fluoro, estradiol was developed as early
4:24
as 1984 in the lab of Dr.
4:27
Ka Bogan.
4:28
Um, and that was developed as the first pet imaging agent
4:31
for a receptor target.
4:32
So far, predominantly the work horse
4:34
and still is the work horse as fluoro doxy glucose,
4:36
but that tracks the glucose metabolism happening
4:39
inside, um, the cells.
4:41
So that's not a receptor targeting agent.
4:43
And then this, uh, was finally approved by the us, uh, FDA,
4:48
uh, in 2020.
4:49
And since it's being used in, in clinical practice,
4:53
a few key points, um, that we have
4:55
to keep in mind when reviewing these scans
4:58
and potentially even earlier when protocoling these scans,
5:01
is that there is substantial interference
5:04
by some estrogen targeted medications on FES pit.
5:08
Most notably the, uh, the serums such as tamoxifen
5:11
and the surges which are complete estrogen receptor
5:14
degraders such as fulvestrant, these have to be stopped
5:17
for these durations.
5:18
And you, you see that for s it's about eight weeks
5:20
because these are estrogen receptor modulators.
5:22
But for receptor degraders, it's as high as 28 weeks.
5:26
And if the patient has received these medications within
5:29
this time gap and FES PET is, is unlikely
5:32
to help an accurate assessment of the estrogen receptor
5:35
because the estrogen receptor is the site of action
5:38
for these medications.
5:40
On the contrary, some other estrogen targeted medications
5:43
such as aromatase inhibitors, commonly anastrozole
5:46
and letrozole and CDK four six inhibitors such
5:49
as palbociclib and ribociclib do not interfere with FES pet.
5:53
And therefore, it's fine to get, um,
5:54
the FES PET even if these medications have been
5:57
initiated recently.
6:00
Moving on to the biodistribution of FES of fluoro estradiol,
6:03
here's a maximum intensity projection image,
6:06
and we will talk about this biodistribution pattern in a
6:09
similar way for the other radiopharmaceuticals.
6:11
Some of the things to keep in mind
6:13
whenever reviewing these tracers, the non ftg,
6:16
the non FDG tracers, is to keep an eye on
6:18
what intensity scale are you looking at.
6:20
So the SUV scale becomes super important, uh,
6:23
in the interpretation of all of these radiopharmaceuticals.
6:26
And as we shall see in the subsequent slides,
6:28
all the tracers cannot be interpreted on the same scale
6:31
as they have a completely different biodistribution.
6:34
So for example, here, the scale is set to nine just so that,
6:37
uh, uh, some of the organs
6:39
or some of the physiologic sites can be shown better.
6:42
So the first prominent thing
6:44
that we see on this maximum intensity projection image is
6:47
this sort of linear areas
6:49
of increased tracer activity along the
6:51
patient's upper extremity.
6:52
And this is one of the hallmarks of FES pet
6:55
because this is the activity that's sticking
6:57
to the injected veins.
6:59
And, uh, whenever you start looking at these tracers,
7:01
start off by looking at the maximum intensity projection
7:04
image first, uh, to kind of make sure that the,
7:06
that the tracer that you're looking, you know, that tracer
7:08
that you're looking at, and you can kind
7:10
of identify it from the bio distribution.
7:12
So this is one of the important things to note.
7:14
It's just the tracer activity
7:15
that's sticking along the injected vessels
7:18
that shows up like this.
7:19
If you're looking at, uh, the transactional images, some
7:23
of these activities might be more focal,
7:25
might appear more focal on that.
7:26
So again, it's important to review the maximum intensity
7:29
projection image and not to confuse these with, um,
7:32
like local nodal lesions, for example, in the xi
7:37
next off talking about the head.
7:38
And as you can see, uh,
7:39
and if you, if you read a lot of ft g pets,
7:42
you'll see a clear, uh, difference between FES
7:44
and FTG in that there is negligible activity in the brain.
7:48
And if you, if you look closely,
7:50
and again, this is not at an SUV scale of nine,
7:53
this is probably at an SUV scale of one
7:55
or two, just to kind of show you how it, how, uh,
7:59
the appearance is in the brain.
8:00
And you can kind of see these white matter tracts
8:03
that have physiologic expression of the estrogen receptors.
8:06
So FES normally is taken up by these white matter tracts.
8:09
And again, this is a physiologic expected biodistribution
8:13
moving on to the more intense organs, for example,
8:16
as you notice on the MIP image, liver is very intense.
8:19
And this is at a SUV scale of nine.
8:21
If you move on to a SUV of 5.5, you'll see
8:24
that the liver is completely blacked out.
8:26
It's hard to even make the differentiation of
8:28
what is liver parenchyma versus what is ducts.
8:31
But if you adjust the scoring, uh,
8:32
the scaling appropriately, you'll find
8:34
that the liver parenchyma does have a lot of activity.
8:37
But then even more intense activity is known along the
8:40
biliary ducts and the gallbladder.
8:42
This is all excreted activity, uh, that happens
8:45
after the metabolization of F-E-S-F-E-S is a steroid,
8:49
um, estrogen compound.
8:50
So it gets metabolized in the liver
8:52
and then all of its metabolites gets secreted
8:54
through the biliary system.
8:56
So all of your bile ducts, the gallbladder, finally,
8:58
the common bile duct duodenum, all of that's going
9:01
to have a lot of excreted activity,
9:03
and they'll appear as, um,
9:05
quite intense on the maximum intensity projection image.
9:08
Finally, as one can realize that once there's a lot
9:11
of biliary secretion of these metabolites,
9:13
our bowel will have a lot of activity,
9:15
and this is all within the small bowel loops.
9:18
So here you can kind of see some
9:20
of the activity in the liver.
9:21
This is the common bile duct, which is, uh,
9:24
eventually gonna drain in the duodenum.
9:26
And then you see some of the, uh,
9:27
activity in the bowel loops that we see here.
9:30
Normally, there is a lot of absorption
9:32
of these metabolites from the small bowel,
9:34
so we don't see a lot of activity in the large bowel
9:36
that would be unexpected.
9:39
And finally, another important site
9:41
to recognize in FES is this normal physiologic uptake in the
9:44
endometrium, and you can kind of see that the activity,
9:47
if you, uh, sort of increase the windowing even further,
9:50
you'll see that this activity nicely localizes
9:53
to the endometrium and not to the myometrium.
9:55
And this is, again, a physiologic expected, um, site
9:58
of FE septic because
9:59
of the estrogen receptor, um, expression.
10:02
Now, if you, uh, uh, if you try to compare this
10:05
with F-D-G-F-D-G in premenopausal women, uh, uh,
10:10
in in patients who are menstruating,
10:11
who have ongoing menses, uh, we see that the, uh, uterus
10:15
or the endometrium can have variable levels of uptake,
10:18
and that's often regarded as physiologic
10:20
unless there are other CT signs which suggest otherwise.
10:23
But in postmenopausal women, we see
10:25
that FT G uptake in the endometrium can suggest a primary
10:29
endometrial malignancy.
10:30
So, uh, again, something that's different from, um, FES.
10:35
Next, we'll review some of the common indications.
10:38
Um, again, these are some of the common clinical indications
10:41
that we encounter, uh,
10:42
in which FES can be a valuable imaging modality.
10:45
So one of the very important, uh, uses of FES is
10:49
to predict response to endocrine therapy.
10:51
Now, once these patients with breast cancer, once they have,
10:55
uh, er positivity based on immunohistochemistry,
10:58
these patients are good candidates
11:00
for estrogen targeted therapy.
11:02
But not all patients do well, even
11:04
after having, even,
11:06
despite having an estrogen receptor positivity
11:08
on their pathology samples.
11:10
And one of the common causes of why this happens is
11:12
because of the tumor heterogeneity.
11:14
Um, the, the lesion
11:16
that was initially biopsied might have had ER expression,
11:19
but its metastatic sites at other sites might not have
11:22
sufficient ER expression to kind of respond
11:25
to that endocrine therapy.
11:26
And because FES PET is, uh, an in-vivo imaging, uh, tool,
11:30
it can, uh, inform us on the estrogen receptor
11:33
expression across the body.
11:34
So it, it's not just telling us about estrogen receptor at
11:38
one site, which is typically
11:39
what happens when you biopsy these lesions,
11:41
but kind of throughout the body.
11:43
And we'll see an example.
11:45
Um, for example, this is a, again,
11:47
if you recognize the biodistribution, you see this intense
11:50
activity in what seems to be the brain.
11:51
This is only skull base to mid thigh,
11:53
but we still see the, this brain activity.
11:56
We see myocardial activity,
11:57
some excreted activity in the kidneys and the bladder.
12:00
So we know that this is FDG or fluoro deoxy glucose.
12:03
So in this patient, uh, who had an ER,
12:06
positive invasive ductal carcinoma,
12:07
she had multifocal osseous metastasis.
12:10
And you can kind of see some
12:11
of those prominent lesions right here, right here.
12:14
Some of the vertebral lesions, iliac lesions,
12:16
so several ous metastasis,
12:18
and it was being considered whether this patient should
12:20
receive endocrine therapy.
12:22
Next, she had progressed
12:23
after an initial, um, endocrine therapy.
12:26
So therefore, an FES PET was ordered.
12:28
And again, if you look at the biodistribution, kind of some
12:31
of the things we talked about, um,
12:33
expected activity along the vein, that
12:35
that's the injected, um, activity.
12:37
And then you see this very intense activity in the liver.
12:40
And in contrast to the case that I showed you earlier,
12:42
I had adjusted the windowing so that you could see the,
12:45
even the intricacies within the liver.
12:47
This is at a much lower scale of around five.
12:50
So the liver appears almost in that blackout.
12:52
We also see some activity, uh, throughout the bowel loops,
12:55
and we have the excreted activity within the bladder.
12:58
But what really is important in this patient is, uh, trying
13:02
to figure out if these lesions are also showing up on FES,
13:05
because that would tell us
13:06
that these are having ER expression
13:08
and potentially this patient could be amenable
13:10
to receiving endocrine therapy.
13:12
But if you look at this, um,
13:14
sagittal sagittal image on the bone window,
13:16
we don't see any, um, significant levels of ER expression
13:20
as highlighted by the FES uptake at these sites.
13:24
And again, for comparison,
13:25
I pulled up the sagittal images from the, uh,
13:28
fused FTG PET ct,
13:29
and you can kind of see that there are multifocal ous
13:32
metastasis within the spine.
13:34
And comparing that to the FES,
13:35
you barely see any tracer uptake.
13:38
So that this tells us
13:39
that even though this patient had er positivity on biopsy,
13:43
since majority of the lesions are not, uh, expressing FES,
13:47
this patient is unlikely to respond to endocrine therapy.
13:50
And we have some data,
13:52
several people have published extensively on this.
13:54
And we kind of compiled this into a systematic review
13:57
and meta-analysis from 12 studies, including 308 patients,
14:02
where we pointed out the very high negative predictive
14:05
value of FES pet.
14:07
What this sort
14:08
of diagram shows us is if the patient is FES negative,
14:12
and by negative, there are different thresholds used.
14:15
But an SUV of less than 1.5
14:17
or SUV of less than two is a common threshold used
14:20
to determine if the patient is going to respond
14:22
or is going to have a clinical
14:23
benefit from endocrine therapy.
14:25
So in patients that are FES negative, the likelihood
14:29
of clinical benefit from endocrine therapy is just one in
14:32
nine or about 11%, which is, which
14:34
as we realize is a really low number.
14:37
Whereas if the patients have FES positive disease,
14:40
which means commonly an SUV of more than 1.5
14:43
or more than two, the likelihood increases significantly
14:47
to about 66% or six in nine patients.
14:50
So again, a patient having a negative FES PET is very less
14:54
likely to respond to endocrine therapy,
14:56
especially when compared to someone
14:57
who has FES positive disease.
15:01
Next, we'll talk about some scenarios where we like to stage
15:04
or rest stage patients with invasive lobular carcinoma
15:07
as well as low grade invasive ductal carcinomas.
15:10
And a lot of you may be aware that, uh, invasive lobular,
15:13
both of these, uh, indications, lobular histology, as well
15:17
as a low grade invasive ductal carcinoma,
15:19
ftg PET has a somewhat lower sensitivity in these patients.
15:23
Lobular histology especially have either very minimal
15:25
or mild FTG ity,
15:26
and it's hard to, uh,
15:28
detect disease accurately in these patients.
15:31
So for an example, we have FTG pet,
15:33
and again, uh, emphasizing on the biodistribution,
15:36
we see the brain activity, myocardium activity,
15:39
kidneys in the bladder, lower level in the the liver.
15:42
So we know this is an FTG.
15:44
Um, so this was a patient with invasive lobular carcinoma
15:47
with rising tumor markers.
15:48
And when we performed the FDG pen, the only site
15:51
that was prominent was this rib.
15:53
And when we looked at the transactional images, we saw
15:56
that there was a clear, um, fracture at that rib,
15:59
and that was the reason why this was showing up.
16:01
Uh, with increased FDG ability.
16:02
The patient also had a recent trauma to that site,
16:05
so clearly not a site of disease,
16:07
but we did not find anything to explain, uh, the,
16:10
the rising tumor markers.
16:13
So because the initial tumor was ER positive,
16:16
we performed an FES pet,
16:17
and you can kind of see these multifocal metastases
16:20
that were not at all seen on the FT G pet.
16:23
Going back to the FTG pet, these only had like a minimal
16:26
or mild FTG avidity not sufficient to call, uh,
16:29
metastatic disease.
16:31
So looking at the, the transactional images here is the,
16:35
the CT image, and you can maybe see a subtle
16:38
sclerotic coate right there,
16:40
but adding on the FES PET really as useful information.
16:44
And this focal increased uptake in this rib, um,
16:47
suggests er expressing tumor cells in there and, and,
16:50
and, uh, um, compatible with metastatic disease,
16:52
as we also see elsewhere in the body.
16:55
Another important thing I'd like
16:56
to point out here is this sort
16:58
of diffuse uptake throughout lungs.
17:00
I haven't added the lung windows, um,
17:03
but, uh, uh, there is some prominence more anteriorly.
17:06
And this is a pattern that you'll commonly see in patients
17:09
who've received radiation in the past
17:11
as radiation pneumonitis.
17:12
Typically, uh, the,
17:13
the radiation related inflammation can lead
17:15
to this diffuse sort of uptake in the lungs,
17:18
especially more prominent anteriorly
17:20
as these patients are being
17:21
radiated for their breast cancer.
17:23
So important not to mistake, uh, you know, not
17:25
to confuse this with a different condition.
17:28
And I also provided a, a comparison image from the FDG
17:31
to kind of look at the same rib.
17:33
And if you're looking at this rib, again, the uptake is
17:36
so low level and so, um, so subtle, it would be really hard
17:40
to call this as a definitively metastatic side on
17:43
the FTG PET alone.
17:44
So FES PET really helps us in these scenarios.
17:48
Finally, characterizing lesions which are difficult
17:50
to biopsy, or in cases of non-diagnostic biopsy, again,
17:54
an FT G pet, and this was a patient
17:56
with invasive ductal carcinoma
17:58
who also had rising tumor markers.
18:00
When we performed the FTG pet,
18:02
we really did not have a definitive site
18:04
to suggest metastatic disease,
18:06
but we did notice some o mental nodularity.
18:09
Now, this augmental nodularity was biopsied
18:11
and turned out to be negative.
18:13
So despite the rising tumor markers,
18:15
we did not have a good site to suggest the site
18:17
of disease recurrence or disease progression.
18:20
So NFES PET was ordered again
18:21
because this patient initially had ER positive disease,
18:24
and we, again,
18:25
have the maximum intensity projection image kind of looking
18:28
for the familiar sites to recognize that this is FES.
18:32
And when we looked at the transaction, it's kind of hard
18:34
to appreciate on the mip, uh,
18:36
but on the transactional images, you see this sort
18:38
of high level tracer activity in the same region
18:40
of the mental no laity that we earlier saw.
18:43
And this is not one of the typical sites
18:46
of FES um, activity.
18:48
So this is very, uh, this has er expression
18:51
and is very highly likely to be, uh, metastatic, uh,
18:54
or mental disease from the patient's primary.
18:56
And another thing that if you closely look at the MIP image,
18:59
there is this focus of uptake here, um,
19:01
which on the trans actuals, uh, corresponded nicely to,
19:06
to a vertebral uh, lesion at the right
19:07
of the transverse process.
19:09
And again, this focal activity,
19:10
which you can also see on the maximum intensity projection
19:13
image suggests you are expressing tumor there.
19:15
Going back to the FDG for the same site, we, it's, again,
19:19
retrospectively you may call something there,
19:21
but it's really subtle
19:22
and really hard to call prospectively.
19:24
So again, another example where these, these sites
19:28
that are difficult to biopsy
19:29
or with non-diagnostic biopsy, FES, can really help.
19:32
And this patient did get a transverse process biopsy from
19:35
this, uh, vertebral body lesion,
19:36
and that was positive for metastatic disease.
19:39
Finally, um, um, uh, er determining the ER status
19:43
to address prior equivocal findings.
19:46
And one of the common scenarios that we see with ftg pet.
19:48
So in this patient who, uh, was also suspected
19:51
to have disease recurrence, um, we saw this, uh,
19:54
bilateral symmetric media sty
19:56
and high lymphadenopathy, quite high, FTG avid, in addition
20:00
to some more, excuse me, um, upper abdominal lymph nodes,
20:04
as well as some lymph nodes in the abdomen.
20:06
Um, uh, again, this pattern as, uh, uh, most
20:10
of you would recognize is very, uh,
20:13
commonly seen in patients with a lot
20:15
of infective inflammatory conditions like sarcoid, a lot
20:17
of grand as infections such
20:19
as histoplasmosis and tuberculosis.
20:21
But we cannot be definitive in patients with, uh, uh,
20:24
rising tumor markers.
20:25
So with su suspect, uh, su suspicious disease.
20:28
So again, we see this mediastinal lymphadenopathy,
20:31
and you can kind of see that they,
20:32
these were intensely FTG avid, so
20:34
therefore, to sort this out
20:35
and to, uh, the patient refused
20:37
bronchoscopy biopsy at that time.
20:39
And FES PET was ordered
20:40
because his, her initial disease was ER positive.
20:43
And you can, again, nicely see on the MIP
20:45
that there is just no correlate for all
20:47
of these mediastinal lymph nodes.
20:49
Some of the upper abdominal lymph nodes would be harder
20:51
to appreciate on the mip,
20:52
but they did not have a correlate either.
20:55
And again, uh, a representative image for FES
20:57
and you just see regular, um, activity, no, uh,
21:00
increased activity related to these mediastinal lesions.
21:04
And then this patient finally agreed to do, to get a bi, uh,
21:07
uh, a bronchoscopy biopsy.
21:08
And this was a case of biopsy proven sarcoidosis.
21:11
So cases where the prior imaging might be equivocal, uh,
21:15
FES PET can really help sort out the next steps
21:18
or help us figure out in which direction are we headed.
21:22
Okay, so time for our next poll.
21:25
Um, which of these sites do not show physiologic tracer
21:28
activity on FES pet?
21:31
And we kind of talked about this a little bit,
21:33
and the options are endometrium, stomach,
21:37
liver, or small bowel.
21:39
And again, we'll wait for like 15 seconds just to make sure,
21:42
or,
21:49
and again, the question asks for which
21:51
of these do not show physiologic tracer activity on FES pet?
21:57
Okay, so really great response,
22:00
and most of you answered stomach, which is the right option.
22:03
And like we discussed
22:05
before, endometrium,
22:06
physiologic uptake in the endometrium is expected
22:08
for FES bed because of the estrogen receptor expression.
22:12
We have a lot of FES metabolization happening in the liver.
22:15
So we saw that the liver was the most intense, um, um,
22:18
physiologic site on ES, and
22:20
therefore detection of liver lesions can be suboptimal just
22:22
because of the high background activity that you get there.
22:25
Um, and that activity is excreted by the biliary system.
22:29
So you also get a, get very
22:30
high activity in the small bowel.
22:32
Again, an important, uh, site to remember
22:34
because patients with invasive lobular carcinoma especially
22:37
can have serosal deposits
22:39
or deposits really close to the small bowel.
22:41
And because of the high background activity there, uh,
22:44
those smaller lesions might be difficult to pick up.
22:46
So important pitfalls there as well.
22:48
Stomach does not have
22:50
or should not have physiology tracer activity.
22:52
Um, so if you're seeing some activity in the stomach
22:55
that's clearly localizing to the walls, it's important
22:58
to think of disease, especially in the setting
22:59
of lobular carcinoma.
23:01
Um, another important pitfall that I'd, I'd like
23:03
to mention here is
23:05
because we have activity going,
23:06
going in the small bowels in the duodenum, uh,
23:09
from the common bile duct,
23:10
if the patient has biliary reflux,
23:12
that is the bile is getting reflux from the duodenum to the,
23:16
to the stomach, you might get some intraluminal activity
23:19
within the stomach just as a result of
23:21
that bilio gastric reflux.
23:23
But that activity will not look,
23:25
should not localize to the gastric walls.
23:27
It should predominantly be intraluminal.
23:29
Alright, um, moving on to the next tracer, uh,
23:33
for today's discussion.
23:34
Uh, somatostatin receptor targeted pet.
23:37
Now somatostatin receptors are g g-protein coupled
23:41
receptors, and there are five major subtypes
23:44
of these somatostatin receptors.
23:46
SST R one to five. The most important receptor subtype
23:49
that we are interested in from an imaging perspective
23:51
is SST R two.
23:53
And that's because, excuse me,
23:55
it's most abundantly expressed on the well differentiated
23:58
neuroendocrine tumors.
24:00
Um, this is a table that just to show
24:03
that there are multiple ways
24:04
of targeting the somatostatin receptor
24:06
and, uh, for example, some of the affinity shown here.
24:09
So the lower the value, the higher the affinity.
24:12
So for example, if you look at gallium dotatate, the,
24:15
for SST two,
24:16
the value the half maximal inhibitory concentration is 0.2,
24:20
which means it has a very high affinity for SST R two, not
24:24
so much for SST R three and five,
24:26
and then some vari, some variation among these tracers.
24:30
But again, the most important tracer
24:32
that we are interested in for majority
24:33
of these well differentiated neuroendocrin
24:35
tumors is SST r subtype.
24:36
Two time for a quick third poll.
24:40
Um, which of these somatostatin receptor targeting pet
24:43
radiopharmaceutical is not currently approved by the US FDA?
24:49
So again, we have a negative question.
24:51
Um, three of these tracers are approved, which one is not,
24:55
and the options are gallium dotatate, gallium dota talk,
24:59
gallium Dota knock and copper dotatate.
25:02
And I promise that all
25:03
of these are alleged
25:04
radiopharmaceuticals, hang on.
25:08
Um, pausing for a little bit here.
25:20
Okay. So, um, I think the most, uh,
25:24
common choice was copper dotatate, followed
25:27
by gallium Dota knock, followed by gallium dota talk.
25:30
No one went for gallium dotatate, which is good
25:32
because I think that's one
25:34
of the most common radio tracers we use.
25:36
Uh, but unfortunately the most preferred option copper
25:39
dotatate is not the correct choice.
25:41
Uh, the correct choice is gallium Dota knock.
25:45
So the first FDA approved radiotracer in this space was
25:49
gallium dotatate, the pet radiotracer in 2016, followed
25:52
by Gallium Dota talk in 2019.
25:55
Gallium Dota talk is more frequently used in the Europe
25:57
than it is in the us.
25:59
Um, we predominantly used Dotatate.
26:01
And then more recently in 2020, um,
26:04
copper dotatate copper 64 labeled Dota date was approved.
26:08
So if you're practicing in the US you're more likely
26:10
to see copper Dota date
26:11
or gallium Dota date, uh, in your clinical practice.
26:14
But, um, gallium dot knock is being used in several parts
26:18
of the world, including Europe.
26:19
A lot of places in Asia, uh,
26:22
however, if you're looking just at the physiologic
26:25
biodistribution visually,
26:27
these tracers have a very similar biodistribution.
26:30
So it's often very hard to kind
26:32
of differentiate these tracers just based on the
26:34
biodistribution, because they're all, um, um, localizing
26:37
to the somatostatin receptors.
26:39
Slight variance in the subtypes that we saw earlier.
26:42
But overall, it's a very similar pattern.
26:45
So moving on to the bio distribution,
26:47
and we have the maximum intensity projection image here.
26:50
Um, and notice that while,
26:55
uh, I, I also added the SUV scale,
26:57
and I've set the SUV scale to 10,
26:59
because again, some
27:00
of these sites might be better seen when you're reviewing
27:03
these images in the clinic, you will frequently want
27:06
to adjust the SUV scales so
27:08
that you're looking at all the appropriate organs in the way
27:11
they should be looked at, right?
27:12
So even when we are looking at Ftg PET
27:14
or any other radiopharmaceutical, we frequently do this,
27:16
especially in areas where anything is appear, you know,
27:19
the darkest, so for example, here, you,
27:21
we are using a color scale of black and white.
27:24
So now if you look at the spleen, the kidneys
27:26
and the bladder, they appear completely black,
27:28
which means that you're at the maximum.
27:30
You're, you are. So the,
27:32
I guess the SUV in these areas is higher than 10.
27:34
So you want to make sure that you adjust the windowing
27:37
appropriately, you increase it to levels until
27:39
that organ can be seen, uh, at a lower intensity of color.
27:43
That's important because some of these, uh, um,
27:46
areas might have lesions
27:48
that are just being masked from this, uh,
27:50
very intense tracer activity.
27:53
So, uh, looking at the maximum intensity projection image,
27:55
first off, we notice that there is this focal uptake here.
27:59
We did not see that with FES.
28:01
Um, we expect to see complete brain activity with FTG pr,
28:06
pretty much nothing with FES,
28:07
just some white matter tract activity
28:09
that you may not see on a maximum intensity projection.
28:12
But on a S SST R pet, we expect
28:13
to see this focal activity sort of in the midline,
28:15
and that's activity localizing to the cellar.
28:18
So the pituitary gland has physiologic SST R expression.
28:22
So we see this focal uptake in the pituitary gland.
28:25
Again, physiologic side expected.
28:28
We also see some lower level activity in the salivary
28:32
glands, let's say on the side of our mouth.
28:34
Moving on, liver activity is, um, quite prominent,
28:39
but not as prominent
28:40
as we saw in F-E-S-F-E-S had liver as the hottest organ.
28:44
Here, that's not the case.
28:45
If you compare the compare visually, the activity in liver
28:49
and spleen, you see that the spleen is
28:50
way more intense than liver.
28:52
So spleen is indeed the site with maximal
28:55
SUVs on an SSTR pet, and that's the way to recognize it.
28:58
The other important thing that I'd point out here is
29:01
that this activity is within the stomach,
29:03
within the gastric walls, again,
29:05
because there is physiologic SSTR
29:07
expression in the gastric wall.
29:09
Now, if you were seeing the same pattern on an FTG pet,
29:12
you might think about, for example,
29:14
gastritis is a frequent culprit.
29:16
Uh, these patients tend to have diffuse varying levels
29:19
of intensity of FDG activity.
29:21
But on a dotatate
29:22
or on an SSGR pet, it's important not
29:25
to call this gastritis again
29:27
because, uh, we expect
29:28
to see physiologic activity at that site.
29:32
Moving down a little bit further,
29:33
and we have these coronal images,
29:35
and you can kind of see the,
29:37
the bilaterally symmetric activity in the supra renal
29:40
regions, and that's the expected activity in the adrenals.
29:44
We are also seeing, uh, a lot
29:45
of activity both in the renal cortex as well
29:48
as in the pelvic EAL system, which, which tells us
29:51
that there is physiologic expression
29:53
even in the renal cortex.
29:54
It's not just the excreted activity that we are seeing.
29:56
So all of this, the physiologic expression in the cortex,
29:59
and then we are seeing some, um, excreted activity,
30:02
and you can kind of see from the maximal intensity
30:04
projection image that we are also seeing this, um,
30:07
activity throughout the bowel loops,
30:09
which we also see, um, here.
30:12
So next, moving on to some of the common indications
30:14
that we see in the clinic for utilization
30:16
of somatostatin receptor targeted pet.
30:19
One of the common ones is staging
30:20
or restaging of pat, uh, patients
30:22
with well differentiated neuroendocrine tumors.
30:26
So, uh, again, going back
30:27
to the maximal intensity projection image, we, uh,
30:30
just look at the biodistribution first.
30:32
We see this focal activity sort
30:34
of in the midline likely activity within the pituitary, uh,
30:37
some salivary gland activity.
30:39
You also see some expected activity in the thyroid.
30:42
Again, important not to, uh, you know, confuse this
30:45
with pathologic activity.
30:46
Uh, the C cells in the thyroid do have somatostatin receptor
30:49
expression, which is responsible for this normal uptake.
30:52
Spleen is the hottest organ.
30:54
We see lower levels in the liver, kidney,
30:57
so extruded activity in the bladder.
30:58
So we know it's a somatostatin receptor targeted pet.
31:01
It could be a gallium dotatate,
31:02
it could be a copper dotatate.
31:04
So this patient, uh, was being staged
31:06
for a well differentiated grade one
31:08
pancreatic neuroendocrine tumor.
31:09
The, the patient had surgery
31:10
before, so this was immediately after surgery.
31:13
We did not notice anything abnormal, no other,
31:16
no focal sites of abnormal SSTR expression
31:19
to suggest metastatic disease at that point.
31:21
So this patient got a staging exam
31:23
and then was just, uh, uh, being followed with, um,
31:26
conventional imaging, um, CT of the abdomen pelvis.
31:30
So eight years later from the initial diagnosis,
31:32
and you'll see this more often
31:34
with well differentiated neuroendocrine tumors,
31:36
because they behave, typically behave in an indolent
31:39
fashion, especially when they're low
31:40
or intermediate grade, they don't metastasize very rapidly.
31:44
And even if they do, the metastatic sites are more
31:46
or less stable for prolonged periods of time.
31:48
So this patient was stable for eight years,
31:50
and then the CT showed some, um,
31:53
hypo attenuating lesions throughout the liver, which were,
31:57
uh, suspicious for hepatic metastasis.
31:59
So therefore, a follow-up do date pet was ordered.
32:02
And if you compare the two maximum intensity projection
32:04
image, you can see that all of these sites which are having,
32:08
and again, you can kind of see the normal
32:10
liver activity right there.
32:12
So if you see that these sites are having a, an activity
32:15
that's markedly higher than that of the liver going
32:18
to the trans actuals,
32:19
because that's what you'll also be looking at.
32:20
Apart from the mip, uh, uh,
32:22
these lesions have markedly high tracer activity.
32:26
And I haven't windowed to a scale where you see the spleen
32:29
with much lesser intensity,
32:30
but if you do, uh, you would see
32:32
that these lesions had activity,
32:34
which is higher than spleen.
32:36
And these were, these had a high attenuating
32:38
correlate on the ct.
32:39
And if you compare that to the dotatate bed from about
32:42
seven, eight years back, there were no liver lesions.
32:45
The liver was both enlarged
32:46
and was involved with, uh, multiple hepatic metastasis.
32:50
And these were biopsy proven, uh,
32:52
to represent metastatic disease from a,
32:53
from a pancreatic primary.
32:57
Uh, next indication is for localization of tumors, uh,
33:02
that do not have a known primary site.
33:04
So, for example, patients found
33:06
to have incidentally detected, uh, lymph nodes
33:09
or hepatic lesions, biopsy proven
33:11
to be neuroendocrine tumor,
33:13
but we don't have a definitive site to suggest a primary,
33:16
and that's important from management perspective.
33:19
So, um, again, maximum intensity projection image.
33:22
Note that I have adjusted the SUV to 20.
33:25
A lot of the prior cases had an SUV of 10,
33:27
so we were really seeing the spleen as all dark.
33:30
But here you can kind of appreciate the more finer details
33:32
in the spleen, the windowing is appropriate.
33:35
Um, so this patient had some incidentally detected
33:38
lymphadenopathy on an abdomen ct,
33:40
and one of the larger lymph nodes was biopsied,
33:43
and that showed a well differentiated low grade
33:45
neuroendocrine tumor based on imaging.
33:47
There was no suggestion of a primary site.
33:50
So therefore, a dotatate PET CT was ordered both
33:52
for initial staging and to figure out if we had, um,
33:56
anything suspicious for a primary site.
33:59
So first off, we see right here are these intensely tracer,
34:03
avid foci activity higher than spleen.
34:05
So, uh, uh, and, and,
34:07
and these were the lymph nodes in the misery, um,
34:10
that were also noted on the prior CT
34:12
when adding the pet image.
34:14
You see that these are all intensely tracer rabbit,
34:16
but there was this an additional focus right here, um,
34:19
in the right, uh, lower quadrant.
34:23
And if you add the, the, the pet image onto the ct,
34:27
you notice that this corresponds nicely
34:28
to a small bowel lesion in the distal ileum.
34:31
So this is compatible with her ileal primary with meta, uh,
34:36
metastatic lymphadenopathy in the missent entry.
34:38
So therefore, uh, donate PET really has a high sensitivity
34:42
for picking up, uh, uh,
34:43
the unknown previously unknown primary sites in patients
34:46
diagnosed with metastatic disease.
34:49
Finally, the indications in the scenario for selection
34:53
of treatment with, uh,
34:54
SSTR targeted radiopharmaceutical therapy.
34:57
We know that LUTETIUM 1 77 DOTA date,
35:00
or more commonly known as lutathera, is an FD approved, um,
35:04
radiopharmaceutical therapy for patients with progressive,
35:07
um, neuroendocrine tumor, typically in patients
35:10
who are progressing despite initial octreotide
35:12
or lanreotide therapy.
35:14
So the first step in that process,
35:16
before you decide, um, to, uh, advise the candidate
35:21
or advise the patient and discuss with them, the suitability
35:23
for therapy is to really see if there is sufficient, uh,
35:26
expression of the somatostatin receptors on the tumor cells,
35:29
because that's the major prerequisite for therapy.
35:32
If you don't have adequate somatostatin receptor expression,
35:35
uh, you know, because lutetium dotatate is again,
35:38
going directly to the somatostatin receptors,
35:40
you would not expect a high efficacy of of therapy.
35:45
So this is a patient who was, who was, uh, being, uh, uh,
35:48
uh, evaluated for consideration of lutetium dotatate therapy
35:52
or lutathera therapy, and the patient had progressed despite
35:56
initial octreotide treatment.
35:57
And again, maximum intensity projection image.
36:00
You see, uh, a small, uh, lesion could be a calver lesion,
36:04
could be an intraparenchymal lesion.
36:06
I'll take this time to emphasize, uh, uh,
36:08
an important differential.
36:10
Um, when you're seeing this activity in the brain
36:13
or even in the, the calvarium, uh, think about meningioma,
36:18
uh, in addition to metastatic neuroendocrine tumor
36:21
and meningiomas tend
36:23
to be more common than metastatic neuroendocrine tumor,
36:25
when, especially when, look, when these lesions are sort of,
36:28
uh, uh, it, it might be hard
36:29
to figure out whether they are in the brain versus really
36:32
close, uh, uh, to the bone.
36:34
And, and r can help us, uh, make that distinction.
36:37
But always think of a meningioma first when
36:39
you're looking at these sites.
36:41
This case, however, uh, did,
36:43
did have metastatic neuroendocrine tumor
36:45
and then there were a lot of axillary lymph nodes diffuse,
36:49
um, liver metastases, some retroperitoneal lymphadenopathy,
36:52
more aous metastasis.
36:54
And so therefore, this patient was being considered
36:56
for lutetium durate therapy.
36:59
Now, when, uh, you take into account different factors,
37:02
but one of the important factors
37:03
to take into account is adequacy
37:05
of somatostatin receptor expression,
37:07
and we figured that out using what's called
37:09
as a modified trending score.
37:11
The initial trending score was described on octreoscan,
37:14
which is not, um, uh, a PET imaging tool.
37:17
Uh, it's using, uh, uh, uh, 111 indium octreotide,
37:22
much lower sensitivity
37:24
and much lower, uh, image quality compared to SSTR pet.
37:27
So the original trending score was developed for that.
37:29
Now we have the modified trending score for SSTR pit.
37:33
Now this takes into account some
37:35
of the normal physiologic sites, which include blood pool,
37:38
and you can kind of see that on this windowing blood
37:40
pool activity is really low.
37:42
That's supposed to be the mediastinal blood pool.
37:44
Um, so zero and one are activity, which is similar to
37:48
or below that of the blood.
37:50
Two is activity that is similar to liver,
37:52
but above blood pool.
37:53
Three is higher than liver, but below spleen.
37:55
And again, we retrade that spleen is the hottest organ.
37:58
So therefore, if the activity is higher than spleen,
38:00
that gets you the highest score of four.
38:03
So, um, let's, let's do that visual comparison here
38:06
and we'll take one of these liver lesions
38:08
as our target lesion.
38:10
So, and again, this is a visual scale,
38:12
so we are not gonna take SUVs into account.
38:14
So this lesion, if we compare it to the liver
38:17
and very, there's a tiny sliver
38:19
of normal liver parenchyma to look at.
38:20
It might be projecting differently, uh,
38:23
and might be easier to do on a transaction,
38:25
but there is a tiny sliver of normal hepatic parenchyma,
38:28
and we can clearly see that this,
38:29
this activity in the lesion is much higher than that of,
38:33
of the, uh, normal liver parenchyma, whatever little bit
38:36
of liver parenchyma there is.
38:38
And if you compare that with the spleen,
38:40
and again, with the windowing adjusted appropriately,
38:42
you see that this activity is also higher
38:44
than that of the spleen.
38:45
So for a case like this, you would assign a score of four,
38:48
which is the highest possible modified training score,
38:50
the activity being higher than that of the spleen.
38:52
And again, this patient, a lot
38:55
of different factors would go into the decision making lab
38:58
features, clinical parameters,
38:59
but purely from an SSTR PET imaging perspective,
39:02
this patient would be a good candidate just
39:04
because of the very high somatostatin receptor expression,
39:07
um, as, uh, evidenced on this imaging.
39:11
Alright, so this brings us to our next poll.
39:14
Um, which of these clinical scenarios would have the least
39:18
likelihood of benefit from treatment with lutetium,
39:21
dotatate, or lutathera?
39:23
Again, the radiopharmaceutical therapy we talked about,
39:25
we are looking at patient, the, the imaging feature,
39:28
which would have the least likelihood
39:31
of, of clinical benefit.
39:33
And your options are number one SSTR positive
39:36
FDG negative lesions.
39:38
Number two is SSTR and FDG positive.
39:41
So positive on both SSTR and FDG imaging.
39:44
Option three is SSTR negative and FDG positive.
39:48
And option four are, there are no differences
39:50
among these scenarios based on an imaging point,
39:53
they would all have similar likelihood of clinical benefit.
40:05
Okay, so we have some people responding to the pulse
40:08
and the clear majority answered SSTR negative
40:12
or FTG positive, um, lesions, which is the right answer.
40:17
And, uh, we'll take a look why.
40:20
So this was a patient who was referred to us for,
40:22
he was progressing on, um, octreotide,
40:25
and he was initially diagnosed
40:27
with a well differentiated
40:28
neuroendocrine tumor of the pancreas.
40:29
It was a grade two, uh, tumor.
40:31
And you can kind of see the tumor right there.
40:33
Uh, not easy to see it on the mip, easier
40:36
to look on the trans actuals,
40:37
but that's, that's the primary, uh, the patient, uh,
40:42
was being treated with octreotide was being followed on, uh,
40:45
abdominal MRIs and CT abdomen pelvis,
40:48
and the abdominal MR MRIs showed new liver lesions that were
40:50
concerning for progressive metastatic disease.
40:53
So this DOTATATE PET CT was ordered,
40:56
and what you can see is, apart from the pancreatic primary,
40:59
the liver is pretty unremarkable,
41:02
and especially in contrast to the case that we just saw,
41:06
maybe there is a slight subtle focus here,
41:08
which is slightly higher than the liver.
41:10
So we can maybe look at the, the, uh,
41:13
transactions more closely.
41:14
But other than that, the liver really,
41:16
really appears unremarkable.
41:19
So given this and the known liver lesions
41:22
and FDG PET was ordered,
41:23
and you can kind of see the remarkable differences in the,
41:26
in these two images on the SSTR pet,
41:29
you barely have any sites that are worth considering
41:33
for metastatic disease.
41:35
But on an FTG pet, you see these multifocal lesions,
41:38
which are very intensely FT g avid.
41:40
The other interesting thing
41:41
that you note here is this pancreatic lesion,
41:43
which was showing up very intensely on dotatate,
41:46
is not showing up at all on FTG.
41:48
And so this patient would not be a good candidate
41:51
for SSTR targeted radiopharmaceutical therapy
41:54
with Lutetium DOTA date just
41:55
because there is really inadequate
41:57
or really negligible SSTR expression on these
42:00
hepatic metastases.
42:02
It's just the pancreatic primary, which is expressing, uh,
42:05
DOTA date and not, uh, uh, uh, uh, not taking up f ftg.
42:10
And this, the, the comparison between SSTR PET
42:13
and FT G PET tells us about the tumor heterogeneity.
42:16
All of these liver lesions are likely
42:18
to behave more aggressively, are likely
42:21
to have a higher grade than this pancreatic lesion,
42:23
which is just showing very intense uptake on SSTR,
42:27
but is not FT G avid.
42:28
So this again, gives us a nice idea about the disease
42:31
spectrum within a single patient.
42:35
Okay, so finally, moving on to the last radiopharmaceutical
42:38
for today's discussion.
42:39
We'll talk about PSMA pet.
42:41
Um, so PSMA stands for prostate specific membrane antigen.
42:46
It's expressed by the folate hydrolase gene
42:49
that's located on chromosome 11 P.
42:51
And this is the structure for PSMA.
42:53
Um, it has, it, it, it, it spans the membrane.
42:56
So it has an intracellular domain that was used
42:59
to initially target this, uh, receptor
43:01
by seven E 11 antibodies.
43:03
One of the major challenges with this approach was,
43:07
and you can kind of see why is if this tumor has an intact
43:11
cell membrane, then this site is not exposed to anything
43:14
that's coming, uh, from externally, right?
43:16
So it's only when the cell membrane is lies is when this
43:20
site is going to get exposed,
43:21
and then you'll have some binding.
43:23
So then attempts were made
43:25
to target the extracellular domain of this,
43:28
uh, uh, receptor.
43:29
And most of the current PSMA, uh, uh,
43:32
PSMA targeting radiopharmaceuticals are targeting this
43:35
active site, which is extracellular.
43:38
Notice that I used the word I, uh, purposefully, uh, uh,
43:43
highlighted the word specific and red.
43:45
And that's because this is a misnomer.
43:47
The, the target is not specific
43:49
to prostate is also expressed in several extra prostatic
43:53
neoplasms, which include both benign
43:55
and malignant tumors, as well as certain
43:58
non-plastic entities in addition
44:00
to the physiologic expected sites.
44:02
And these are common sources of imaging pitfalls.
44:06
Alright, so time for the next poll.
44:08
And I'm asking a lot of negatives today,
44:10
continuing with that trend.
44:12
Um, which of these PSMA targeting PET radio pharmaceuticals
44:15
is not currently approved by the US FDA?
44:18
So carrying on the theme of negative, which
44:21
of these is not currently approved
44:24
and the options are gallium PSMA 11, gallium PSMA,
44:28
INTF 18, D-C-F-P-Y-L,
44:31
and F 18 rhp SMA 7.3.
44:34
You may be more familiar with their, um, brand names,
44:38
but I intentionally included just the generic names.
44:41
Uh, it, it's important for us to know the generic names.
44:53
Okay, so, um, let me see.
44:57
So the vast majority answered R-H-P-S-M-A,
45:01
and that was followed by an equal split
45:04
between P-S-M-A-I-N-T
45:06
and PYL followed by least preferred option PSMA 11.
45:11
Um, the, the, the right answer is gallium P sm A INT,
45:16
all the other three agents, P SMMA 11, D-C-F-P-Y-L
45:20
or R-H-P-S-M-A are all approved by the us FDA rhp.
45:24
SMMA 7.3 is, uh, uh, commercially, uh, marketed
45:29
as pos Luma, D-C-F-P-Y-L Sify.
45:33
P SMMA 11 has several different, including IUs,
45:35
but psma, INT, uh, gallium PSM IT is not currently approved
45:39
by the US FDA.
45:42
Okay, so next on, we'll look at the PSMA pet,
45:46
the bio distribution of of targeting.
45:48
And a lot of these tracers, the ones that I talked about,
45:51
um, have certain commonalities,
45:54
but they also have some differences.
45:55
For example, R-H-P-S-M-A typically has a much lower level
45:59
of bladder activity compared to gallium PSMA
46:02
and F-A-D-C-F-P-Y-L.
46:04
But on, on a broad basis, they have some similar patterns
46:07
that we are, that we look at.
46:09
So first off, if you're looking at the head
46:11
and neck region, again, just go back to what we saw for FES
46:14
and what we talked about in cases with DOTA date.
46:17
Um, FES pretty much had a, had an empty, uh, brain, uh,
46:21
no uptake in the brain at all on the mip.
46:23
Um, with SSTR, we saw that focal uptake in the midline,
46:26
which was the pituitary activity.
46:28
PSMA, again, it's kind of a similar thing.
46:30
We don't see any activity normally.
46:32
So next, when we look at sort of the head
46:34
and neck region, we see this, uh,
46:36
up increased uptake in the salivary glands, uh,
46:39
which sit on the side of the mouth,
46:41
the parotid submandibular.
46:43
We also see expected activity in the lacrimal
46:45
glands going more down.
46:49
Uh, we see this, uh, liver and splenic activity.
46:52
The liver activity is variable.
46:54
Different tracers may have different levels
46:56
of tracer activity, but this is
46:57
what we usually see with PYL.
46:59
Um, renal activity, you see a lot of intense, uh,
47:02
renal cortical activity.
47:04
Sort of similar with what we saw with SSTR.
47:06
Uh, there is, there is renal cortical binding in addition
47:09
to renal excretion.
47:11
And you can see
47:12
that the renal excreted activity is within the bladder.
47:15
And then you see some, uh,
47:16
physiologic activity in the small bowel loops right there.
47:20
So because the kidneys and the urinary bladder
47:22
and the ureter have a lot of excreted activity,
47:25
the kidneys have a lot of specific, uh,
47:27
cortical activity as well.
47:29
Any lesions that are going to be close to these sites,
47:32
you should pay special attention
47:33
and you should frequently adjust the SUV scale.
47:35
So, for example, anything that's closer to the bladder, just
47:38
because of that high background, it might be not,
47:41
not the easiest to differentiate, you know, to kind
47:44
of pick up that small node in that region.
47:46
And the same goes for the ureters.
47:49
So we'll talk about some of the common indications
47:51
for which we use PSMA pet.
47:53
Um, we use it for initial staging of patients
47:55
with unfavorable, intermediate,
47:57
or a high risk prostate cancer.
47:59
And we have an example,
48:01
this is not A-P-S-M-A pet, as you can tell.
48:03
Uh, a 72-year-old gentleman, a PSA of 30, just diagnosed
48:07
with a Gleason four plus four equals eight adenocarcinoma.
48:10
He got a bone scan.
48:11
The bone scan didn't really show anything.
48:13
There was just site of subtle uptake in the rib, uh,
48:17
which had a correlate on ct.
48:18
It was an old fracture,
48:19
but other than that, there was no nothing
48:21
to suggest distant metastasis.
48:24
Now bring PSMA PET into picture
48:27
and we again see this expected biodistribution, lacrimal,
48:30
parotid, submandibular, salivary glands, liver, spleen,
48:34
very high activity in the, uh, renal cortex,
48:36
physiologic activity throughout the small bowel,
48:39
and some activity in the prostate, which again is compatible
48:42
with the known adenocarcinoma.
48:44
The bladder activity is really low in this case,
48:47
but what we see in addition to all of that is this sort
48:50
of solitary focus of tracer uptake here.
48:53
Now on the maximum intensity projection image,
48:55
these sites should make you concerned
48:58
and you should really pay close attention
49:00
to these sites when you look,
49:01
when you're reviewing the transaction images.
49:04
So bringing in the transactional images into the picture,
49:06
you can kind of see this nice focal tracer uptake in the
49:10
left lamina of this, this was the L five vertebra,
49:13
but really no good CT correlate.
49:16
So the CT was read as negative,
49:17
but then when you add on the PET finding,
49:20
this is really focal
49:21
and really concerning for metastatic disease.
49:23
And this was subsequently biopsy proven
49:25
to represent metastatic prostate adenocarcinoma.
49:28
So what, at this point,
49:29
what you really did was you upstage the patient from just
49:32
having localized disease
49:34
and potentially a candidate for definitive therapy,
49:36
either surgery or radiation,
49:37
and you upstage the patient to oligometastatic uh, disease.
49:43
Next off, we use PSMA PET frequently
49:45
for evaluating for biochemical records.
49:47
Um, patients who receive an initial definitive therapy,
49:50
maybe surgery, maybe radiation, uh,
49:53
once they have rising levels of PSA, we want
49:55
to detect the site to explain, um,
49:57
the PS PSA rise and to guide therapy.
49:59
So this was a patient who had a ct,
50:02
the CT was red as negative.
50:04
We can kind of see a normal sized common iliac node, uh,
50:07
common iliac lymph node right there.
50:09
Nothing to suggest
50:10
that it may involve snot enlarged does not
50:12
appear, um, pathologic.
50:13
But when you bring in two picture PSMA pet, you see
50:17
that this clearly has focal ability, uh, uh, in the node.
50:20
And if you compare it to the adjacent vessel, it's,
50:22
it's markedly higher than that,
50:24
at least moderately higher than that,
50:26
and higher than the background as well.
50:28
So this would be concerning for metastatic disease
50:30
to the common iliac node.
50:31
And this was radiated, uh, uh, by external beam.
50:34
And the patient had a PSA response
50:36
of more than 70% confirming
50:38
that this was indeed a metastatic deposit.
50:41
Um, and an important point from an initial staging
50:44
perspective, not so much in the biochemical records setting,
50:47
but if you, if this was a patient who was being scanned
50:50
for initial staging, if you had lymph nodes in the common
50:52
iliac region, those would constitute distant
50:55
metastatic disease.
50:56
So any lymph node that's at
50:58
or above the common iliac station or at
51:01
or below the inguinal station that does not,
51:04
that no longer is regional nodal metastasis,
51:07
that becomes a distant metastasis.
51:09
Another example of a, of, of patient being evaluated
51:12
for biochemical recurrence, um, PSA was around one, um,
51:16
and the patient, uh, uh, had a negative, um,
51:19
um, prior imaging.
51:21
So PSMA PET was ordered.
51:22
And again, apart from the physiologic sites,
51:24
you see this clear focal activity right there that should
51:28
make you very suspicious.
51:29
And when you review the, the transactionals, if you go
51:32
to this site, there is this focal very intense tracer
51:35
activity in the vertebral body.
51:37
Now, if you look closely, and this may not be projecting the
51:40
best way, uh,
51:41
but you see a subtle sclerotic correlate right there.
51:44
This was not called out on the initial ct n it's,
51:46
it's a really hard call.
51:47
There's just a very subtle sclerosis,
51:50
and this was, again, biopsy proven, um,
51:52
to be metastatic disease.
51:54
So now if the, if, if the p if the,
51:56
this patient did not have A-P-S-M-A pet, typically
51:59
what these patients get are either androgen deprivation
52:02
or salvage radiation to the pelvis.
52:04
Now we know that since the lesion is outside of the pelvis,
52:07
androgen deprivation might, might do him some good,
52:10
but just salvage radiation
52:11
to the pelvis will not help this patient at all just
52:14
because his disease is outside that field.
52:16
Um, another important pitfall that I'd like
52:18
to bring up here, not for this case,
52:20
is we frequently see this very subtle, um, sort
52:24
of low level tracer activity in the ribs, um, which may
52:28
or may not have a slight sort
52:30
of ring sclerosis kind of a correlate.
52:32
They might not have a correlate at all, important to be wary
52:35
of calling these isolated rib lesions as metastatic disease
52:38
as the, more often than not these are typically benign.
52:41
Um, and these are typically like fibrosis lesions which have
52:44
a low level of tracer activity, excuse me,
52:48
and a pitfall,
52:53
um, and a pitfall on PSMA pet.
52:55
So if you're seeing these solitary rib lesions
52:57
with minimal traceability, important to be, uh,
53:00
important to recognize this.
53:03
Alright, so finally we also do PSMA PET
53:06
for PSMA determining candidacy
53:09
for PSMA targeted RADIOPHARMACEUTICAL therapy.
53:11
And just like we saw with SSTR pet, um, we use that imaging
53:15
to sort of serve as a foundation
53:17
for figuring out if there is sufficient receptor expression.
53:20
Um, same thing we do with PSMA PET because, uh, Pluto
53:23
or LUTETIUM 1 77 PSMA 6 1 7 is an approved U-S-A-F-D-A
53:28
approved, uh, radiopharmaceutical therapy
53:30
for patients with prostate cancer.
53:32
So to, to treat that patient with uh, uh,
53:36
PSMA targeted therapy, you first need
53:37
to figure out if there is sufficient receptor
53:40
expression and the tumor sites.
53:43
And this kind of brings us to the,
53:44
I'll just briefly talk about the brief concept
53:46
of theranostics, where you have a common, um,
53:49
receptor in this case PSMA,
53:51
and you can use the same target for imaging.
53:54
So you, you have A-P-S-M-A targeting ligand that's bind, uh,
53:57
that's, uh, bound to an imaging radionuclide.
54:00
So for example, gallium 68 or F 18, uh,
54:03
and that's used for imaging,
54:04
but when you switch out,
54:05
switch out the imaging radio nuclide, for example,
54:08
with a beta emitter
54:09
or an alpha emitter, uh,
54:11
that same target can next be used for therapy.
54:13
So it's utilization of a common target
54:15
for both imaging and therapy.
54:17
Uh, and this is a schema that shows us
54:20
how PSM a targeted therapy really, uh, the sort
54:23
of the workflow you have this pre therapy imaging
54:26
where again, you're determining adequate levels
54:28
of receptor expression.
54:30
Uh, some patients might also need an ftg pet like we saw
54:33
with, uh, the prior example with SSTR and ft g.
54:35
So if there are lesions which do not have PSM expression,
54:39
but are showing up on ftg, those would likely not respond
54:42
to, um, PSM and targeted therapy.
54:44
So again, looking at
54:46
that PSMA PET imaging from a therapy perspective, uh, is,
54:50
is is really important.
54:51
Um, okay, so final poll question.
54:55
Um, which of these tissues
54:57
can mimic nodal metastases on A-P-S-M-A pet?
55:02
And your options are hemangioma, uh,
55:05
fibro ous lesions, neural ganglia, and meningioma.
55:18
Which of these tissues can mimic nodal metastases on
55:21
A-P-S-M-A pet, which means that they would have some level
55:24
of tracer morbidity and can
55:26
therefore look like a metastatic lymph node.
55:32
And this is the final poll for the day. Okay.
55:35
So, um, we had an equal split
55:37
between fibro osseous lesions and neural ganglia.
55:40
I purposefully included all of these differentials
55:42
because all of these are known pitfalls with PSMA pet,
55:46
meaning that all of these, uh, sites
55:49
or all of these types, lesions
55:51
or tissues can, um, um, uh, be, uh, PSMA avid.
55:56
Now, the, the, the reason why neural ganglia is the answer
56:00
is because when you look, uh,
56:02
on a maximum intensity projection image,
56:04
we see the symmetric activity most prominently in the, uh,
56:08
upper celiac ganglia.
56:09
We also see it, um, in the cervical ganglia,
56:13
and we also see it in the abdomen,
56:14
in the Celia ganglia, the sacral ganglia.
56:17
These are more often than not more linear,
56:19
more bilaterally symmetric,
56:20
and important to differentiate these from nodes.
56:23
Sometimes they may appear a little bit more nodular,
56:26
but if you're seeing one ganglia,
56:28
you might see more ganglia throughout the body, which again,
56:30
sort of helps us differentiate a ganglia
56:32
from a metastatic node.
56:34
All of the other lesions are hemangioma meningioma fibrosis
56:37
lesions also show up tracer uptake on A-P-S-M-A,
56:40
but they really don't mimic nodal metastases.
56:44
They can mimic, for example, bone metastases, uh,
56:47
or a intracranial metastasis in case of a meningioma.
56:51
Okay. So that was all.
56:54
Um, I'd really like to thank all of you, uh, for joining in,
56:58
for being so interactive throughout the polls.
57:00
I really appreciate it. Um, I'd also like
57:03
to thank the organizers for inviting me,
57:05
and I'm happy to take any questions.
57:08
Yes, thank you so much
57:09
for your lecture you shared with us today, Dr.
57:11
Parr. Uh, yes.
57:12
This time we will open the floor
57:14
for any questions from our audience,
57:15
and you may submit your questions
57:16
through the q and A feature.
57:19
Uh, Dr. Parra, if you're able to pull up that q
57:22
and a box, it's got the little question mark. Word?
57:25
Yes, I gimme one second. I see it.
57:30
Okay. So the first question that I see is how
57:34
to recognize brown fat activity and normal muscle activity.
57:37
That's a, that's a great question.
57:39
Um, that's, uh, very relevant for FTG pet.
57:43
We know that, uh,
57:45
brown fat can have very intense ft g uptake predominantly in
57:49
younger women kids,
57:50
and especially in very cold environments.
57:52
All of that leads to brown fat activation.
57:54
Um, the key really is to sort of first off start
57:58
by looking at the maximum intensity projection image.
58:00
We kind of typically see a nice bilateral asymmetric pattern
58:04
throughout the neck, uh, the mediastinum, upper abdomen, uh,
58:08
sort of the, the supra renal region.
58:11
We start off by doing that,
58:12
but again, a lot of patients
58:13
with lymphoma can have a similar appearance.
58:16
So next we look at the transactional images.
58:19
You want to make sure that you're looking at the same,
58:21
like the PET and the CT images are nicely registered.
58:24
And then once you fuse
58:25
and unuse those images, you can see that the,
58:27
the ftg activity is really localizing to the fat, um, and,
58:31
and, and not, you know, uh, uh, pathologic lymph node,
58:34
for example, or, or, or, or a muscle.
58:37
So that really helps us sort those two issues.
58:39
And it can be a challenge several times,
58:41
especially in patients with lymphoma at the
58:43
times of response assessment.
58:45
So if it's, if it's really a big confounder, uh,
58:48
we also recommend pretreatment
58:50
with a beta blocker like propranolol
58:52
that can really suppress, uh, that brown fat activity
58:55
and really, you know, increase the accuracy
58:57
for detecting lesions on those sites.
59:01
Okay. So let me, okay,
59:05
so the second question I see is, is there specific
59:09
location of brown fat?
59:10
And I kind of talked about it already.
59:12
Uh, so bilateral cervical supraclavicular regions, uh,
59:17
are the most common sites, upper mediastinum, uh, uh, uh,
59:21
uh, uh, upper abdomen, uh, sort
59:23
of the bilateral senal regions,
59:26
right along the paravertebral region
59:28
where you have the sympathetic channels,
59:30
those are the common expected sites, um,
59:32
for brown fat activity.
59:36
Um, okay.
59:37
So the next question I see is, um,
59:42
how to report the prostate lesion.
59:44
Is it possible to recognize peripheral zone basal mid
59:48
gland levels, et cetera?
59:49
That's a great question.
59:50
And, uh, when we are interpreting PSMA pets, we, uh,
59:55
use the scoring system, which, which, which is described,
59:58
uh, in the promise system or the primary.
60:00
We are looking at the primary tumor itself.
60:03
So normally what we do is we look at the prostate
60:05
and multi planees, we just don't look at the transactions.
60:08
We also look at the, the sagittals and the coronals,
60:11
and then it can be easy.
60:12
It's not, uh, like the most definitive
60:14
of things on a PET ct,
60:16
but it can be useful to divide the prostate into sort of,
60:19
uh, three equally spaced regions,
60:22
especially on the sagittal view.
60:24
And then you can kind of figure out
60:25
where the lesion is within the base, sort of mid
60:28
and apical gland.
60:29
Uh, another important thing that I'll add here is, uh, uh,
60:33
seminal vesical activity is to be frequently recognized
60:37
as semial vesicle involvement.
60:38
Can, you know, you, you may,
60:39
you may see like focal activity, which,
60:41
which can be discrete
60:42
or can be contiguous from the prostate lesion.
60:45
Uh, so it's important to recognize that
60:46
because semial vesicle, uh, extension
60:48
of the semial vesicles is important
60:50
from a treatment perspective.
60:53
Um, so the next question I see is, uh,
60:55
do you do baseline FTG PET prior to DOTATATE
60:58
and PSMA therapy to look for discordance?
61:00
Um, it's a very, uh, uh, i I guess
61:05
practice dependent, uh, like the clinical site dependent,
61:08
uh, uh, practice.
61:09
A lot of sites do perform FTG PET pair FT G and SSTR
61:14
or PSMA PET prior to these therapy determination.
61:17
We do not, uh, we, uh, look for, uh, uh, there,
61:21
there are like some cases where we do opt to get
61:24
that added FT G PET in addition to SSTR or PSMA.
61:27
Uh, so for example, pointers that may, uh, you know,
61:30
suggest requirement of, of, uh,
61:32
FTG are if you're seeing an obvious lesion on ct,
61:36
for example, the CT part of PET CT or a prior contrast CT
61:39
or abdominal MRI that we are not seeing on PSMA
61:42
or DOTATATE pet, uh, that's where we, we like to think
61:45
of something more aggressive
61:46
and we like to order FTG pet, uh, patients with sort
61:50
of like higher range of intermediate grade
61:53
or high grade neuroendocrine tumors.
61:55
We may order FT G PET
61:56
because they might be sites
61:57
that we are not seeing on a DOTO date pet
61:59
that might be FT G average.
62:00
So like it's more scenario specific rather than a,
62:03
a universal approach that we adopt.
62:05
But great question. Um, so the next one is,
62:10
is there any estrogen radiopharmaceutical that can be used
62:13
for treatment for the estrogen sensitive tumors?
62:15
That's a, that's a great question.
62:16
Um, uh, there are none that are FDA approved as of now.
62:20
There are different targets actually in breast cancer
62:22
that are being explored, uh, uh,
62:24
for radiopharmaceutical therapy.
62:26
Uh, one of the ones is somatostatin receptors
62:28
because a lot of breast tumors also have somatostatin
62:31
receptors and you have to assess that on, on a dototate pet.
62:34
So again, you know, sort of that combined, uh, imaging
62:37
and therapy theranostics approach you can then use
62:39
to target, uh, those patients with lutetium Tate,
62:42
for example, again, in a non, in a,
62:44
in a clinical trial setting, not in a, not
62:46
as a clinical standard of practice.
62:48
Um, uh, the next question is what is SUV scaling
62:51
for FTG DOTE and PSMA you use?
62:53
That's a, that's a great question.
62:55
I really love it and I emphasize, uh, this on,
62:59
on every sort of lecture that I take
63:01
and during my reading rounds is you really have
63:03
to be very flexible with your SUV scales on an FT GI usually
63:07
start out at an SUV of five or 5.5,
63:10
and then I adjust them multiple times.
63:13
So for example, if I'm looking at the brain, you know
63:15
that the brain is gonna be the hottest, uh, one
63:16
of the hottest sites on an FTG.
63:18
So you really have to window up
63:19
and go as high as you need to so that you're starting
63:22
to see those areas of gray
63:24
and you're able to like delineate, uh, that organ.
63:27
Well, same thing in, in case of FDG, the same thing
63:29
for bladder, uh, kidneys.
63:31
Anything that's at the higher mark, you adjust it.
63:33
For DOTA date, I predominantly operate at SUVs of 10 to 15.
63:39
Uh, again, that really depends on the clinical indication.
63:41
For example, carcinoids do not have very high,
63:43
may not have very high somatostatin receptor expression,
63:46
so you may need to go low as well.
63:47
But for most well differentiated gastro pancreatic
63:50
neuroendocrine tumors, uh, that are well differentiated
63:53
and low grade, you, you'll typically notice
63:55
that they have SUVs ranging in, you know, twenties
63:58
to forties or even higher.
63:59
So then you operate at a higher SUV scale of
64:02
around 15 to 20.
64:03
So, um, um, yeah, and,
64:06
and the same thing for PSME, really,
64:08
really dependent on the scenario.
64:10
If I'm looking for biochemical recurrence, I'll really,
64:13
you know, lower down the windowing even below five,
64:16
like even a two or around two
64:18
or even lower, just
64:19
to make sure I'm not missing a subtle lesion.
64:21
Uh, if I'm looking at sites
64:23
that have very high PSM expression, for example,
64:26
the u not PSM expression,
64:27
but PSMA activity, for example, the ureters, the bladder,
64:30
the kidneys, I'll,
64:31
I'll adjust the windowing appropriately just
64:33
to make sure I'm not being, uh,
64:35
there's no blooming effect on, on uh, adjacent lesions.
64:38
So yeah, very dynamic use
64:40
of SUV V scales, but great question.
64:43
Um, so the next question talks about SUVs
64:46
and, uh, software measurements.
64:47
So SUVs, uh, I mean for most of the, the reading softwares
64:51
that we use, uh, in, in the clinic they have this, um,
64:54
SUV measurement, you can have different type of SUVs.
64:56
So the most common one is SUV maximum,
64:59
and that's the one we use most commonly.
65:01
But we know that there are different types
65:02
of SUV including SUV peak SUV mean, not
65:05
that frequently used in the clinic,
65:07
but they are used in the research setting
65:08
and they might need some, you know,
65:10
some tweaks in the, in the software.
65:13
Um, so there is, uh, FES radiotracer for ER positive lesions
65:17
that is FD approved for breast cancer.
65:20
Yes. So the, the F fe, the flu estradiol labeled with F 18,
65:24
uh, is F US FDA approved
65:26
and uh, uh, it's commercially available in the US as ana,
65:30
it's marketed by GE Healthcare.
65:32
Um, and yes, it was approved in 2020 by the US FDA, so
65:36
that's for targeting ER positive lesions bi.
65:40
Alright. Um, next one is
65:41
how confident reporting FDG AVID positive
65:45
and if ES negative
65:46
as ER negative disease versus false negative?
65:49
That's, uh, outstanding question.
65:51
Um, I kind of, uh, I just try to show some
65:54
of the more representative cases,
65:56
but what we sometimes see is we are seeing some lesions on
66:00
FDG, uh, like for example, the, the case with mediastinal
66:03
and high lymphadenopathy I showed now there my, so
66:07
for example, we saw that FDG picture, we saw
66:10
that FES was completely negative.
66:12
Now from a very, uh, theoretical perspective
66:15
that the FES PET interpretation
66:16
could mean one of two things.
66:18
The first thing is that might not be, um, uh,
66:22
tumor, so it's something else.
66:24
In that case it was sarcoid,
66:25
so it's not tumor, it's something else, right?
66:27
The second thing to think about is it's ER negative, right?
66:32
So it could still mean
66:33
that there is er negative metastatic disease.
66:35
You can never rule out er negative metastatic
66:37
disease at that site.
66:38
And that goes for, for FES PET in general, if the t if the,
66:42
if the tumors are not ER positive,
66:44
they're not gonna show up on FES, then
66:46
what really helps us is the overall clinical picture.
66:48
The tumor markers, the sort of imaging presentation.
66:51
So in that patient with mediastinal
66:53
and OID lymphadenopathy, that pattern is, you know,
66:55
very classical one we see with granulomatous disease.
66:58
So that's why we were more comfortable, you know, saying
67:00
that, hey, this disease is not, uh, showing up on FES.
67:04
Uh, so it's not, it, it does not have any ER expression,
67:06
but we likely think that this is, you know, a ous disease.
67:10
But if it was, for example, a different site for,
67:12
for example, a big auxiliary lymph node, you know,
67:14
in a patient with breast cancer, then I would not be
67:16
that confident in calling that, hey, this is not disease,
67:18
but it, it could very well be er, negative disease.
67:21
So in those cases you really need
67:23
to biopsy and, and figure that out.
67:24
So yeah. Great, great question.
67:28
Alright, excellent.
67:30
I think you got through all the questions that were the in
67:32
through the q and a chat Dr.
67:34
Parr. So thank you so much.
67:36
Thank you everyone, I really appreciate it.
67:39
And thanks to all of you
67:40
for participating in our noon conference
67:42
and asking great questions.
67:44
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67:46
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67:48
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67:49
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67:53
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67:55
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67:58
Bajas will deliver a lecture entitled Imaging
68:00
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68:02
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