0:02

Hello and welcome to Noon Conference hosted by MRI online.

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3 00:00:06,090 --> 00:00:07,740 In response to the changes happening around

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the world right now and the shutting down of

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in-person events, we have decided to provide free

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noon conferences to all radiologists worldwide.

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Today we are joined by Dr. Ivandize.

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Dr. Ivandize is a neuroradiologist slash nuclear

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medicine physician at the Weill Cornell Medicine.

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Her research focuses on CNS molecular

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imaging and the development of novel MR-based

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approaches to blood-brain barrier imaging.

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A reminder that there will be a Q and A session

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at the end of the lecture, so please use the

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Q and A feature to ask your questions, and we will

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get to as many as we can before our time is up.

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That being said, thank you all for joining

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us today. Dr. Ivandize, I'll let you take it from here.

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All right.

0:52

Hi everyone.

0:54

Um, my name is Jana Ivandize, and I'm

0:57

a radiologist at Weill Cornell.

0:59

And, uh, we will be speaking today about

1:02

somatostatin receptor-targeted PET MR and

1:04

PET CT, and I look forward to discussing

1:08

any questions you have on the topic.

1:10

Um, you could just post them

1:12

in the Q and A as we go along.

1:15

So these are some disclosures related

1:17

to, um, clinical trials we're conducting

1:20

that are investigator-initiated.

1:24

Um, so just a couple definitions to

1:27

start out, and this talk is, as we will

1:30

discuss, there are multiple types of, um,

1:32

somatostatin receptor-targeted PET tracers.

1:36

Are now approved.

1:36

Uh, this will be, the cases will all be

1:39

Gallium-68 Dotatate because that's what's

1:41

been in clinical use, uh, for the longest

1:44

in the US as far as PET tracers go.

1:48

Um, so Gallium-68 Dotatate is a PET radio-

1:50

tracer, um, the Gallium-68 as the positron

1:53

emitting part, uh, similar to, um, F-18, which

1:57

is, um, the positron-emitting radionuclide in

2:01

FDG, the more commonly used PET radiotracer.

2:06

Gallium-Dotatate is a somatostatin analog, and it

2:09

binds, uh, with high specificity, um, SST2A,

2:13

which is one of, uh, the five somatostatin receptors.

2:17

And this is, um, what the molecule looks like.

2:20

We have the radionuclide, Gallium-68, which is,

2:22

um, linked via DOTA chelator to the TATE part,

2:26

which is, um, a somatostatin analog Octreotate.

2:30

That's what binds the SSTR receptor.

2:33

It has a high diagnostic accuracy

2:35

for neuroendocrine tumors.

2:36

This is, uh, what a typical, um, maximum

2:39

intensity projection image looks like

2:41

of a Dotatate PET in a normal subject.

2:44

So the highest avidity you can see is in the spleen,

2:47

adrenal glands, um, also in the kidneys, bladder.

2:51

Um, there's also avidity in the pituitary gland.

2:54

And then to a lesser degree,

2:56

we also see physiologic avidity in the

2:58

liver, salivary glands, and thyroid.

3:00

And the GI avidity is variable.

3:03

The principle is similar to, um, Indium-111

3:06

Octreotide, um, which has been around for decades.

3:10

Um, however, several key differences

3:13

and advantages as far as the DOTA PET.

3:16

Um, so the, the.

3:18

Being a PET tracer, it has a higher resolution

3:21

and lower, um, you know, better signal-to-

3:23

noise ratio, lower background, um, activity.

3:27

Um, as there's, it has a higher sensitivity and

3:30

specificity, which is in part attributable to Dotatate

3:34

binding specifically the SSTR2, whereas Octreotide

3:37

binds multiple somatostatin receptors, and SSTR

3:41

2 is the one commonly overexpressed in tumors.

3:45

Um, also the radiation dose is actually lower

3:47

with Dotatate PET compared to Octreotide.

3:49

It's less cumbersome because the patient

3:51

doesn't have to come back for delayed imaging,

3:54

and it's actually more cost-effective.

3:57

This is a comparison from an excellent

3:59

review article, if you're interested.

4:01

I highly recommended it in Radiographics,

4:03

2015, uh, about Dotatate PET Imaging.

4:06

And this demonstrates a patient with

4:09

metastatic neuroendocrine carcinoma, um,

4:12

where you can see a metastatic lesion here.

4:14

This is the Octreotide, um, graphic image, and

4:17

this is the corresponding DOTA PET image, so you can

4:20

see much better, um, target-to-background ratio.

4:24

With delineation of numerous metastases.

4:27

So currently we have Gallium-68 Dotatate, um,

4:31

which has been approved for several years,

4:33

and Copper-64 Dotatate, which

4:35

just recently has been approved.

4:37

The two agents are considered equivalent and are

4:40

now both part of the clinical standard of care,

4:42

as are agents such as DOTATOC and DOTANOC.

4:45

Um, mostly Gallium-68 labeled are in use for

4:48

research in the US and are more widely used

4:50

in Europe and other parts of the world.

4:54

So indications for DOTA PET CT, um, importantly,

4:58

neuroendocrine tumor evaluation, especially GI

5:01

tract, but also other neuroendocrine tumors.

5:03

For example, lung carcinoid.

5:06

Um, evaluation of multiple endocrine

5:08

neoplasia as well as NET of unknown primary.

5:11

And it's also helpful in determining, uh,

5:14

candidates for PRRT, which we'll talk about.

5:17

So specifically, um, Lutetium-177 DOTATATE, or Lutathera.

5:23

Other indications that have found, um, their way into

5:26

more widespread clinical use.

5:28

More recently are, um, evaluation of paraganglioma,

5:31

and anaplastic neuroblastoma, as well as

5:34

increasingly, um, certain subtypes of thyroid cancer.

5:38

And then currently, sort of more in a research

5:42

setting, but, uh, emerging applications.

5:45

And now there are multiple publications validating

5:48

the utility in, um, meningioma and,

5:51

to a lesser degree, pituitary adenoma,

5:54

and to an even lesser degree, lung cancer.

5:57

Hemangioblastoma also expresses

5:59

somatostatin receptors, so it can

6:00

also be used for this indication.

6:03

But meningioma is, um, so Dotatate PET imaging

6:07

in meningioma is a focus of research for me.

6:11

So some of the cases I'll share with you today

6:13

will be focused on that, but it's still not in

6:16

widespread clinical use for this indication.

6:20

As far as interpretation, this is from that

6:22

same Radiographics article I mentioned earlier.

6:25

There's something called the Krenning Scoring

6:27

System, which has to be taken with a grain of salt

6:30

because it was developed for Octreotide scans.

6:34

So it can't really be translated one

6:36

to one, but it's certainly helpful to

6:39

compare to the liver and spleen, since

6:41

those always demonstrate physiologic avidity,

6:45

um, you know, moderate to moderate and

6:47

high respectively for liver and spleen.

6:50

So it's helpful to kind of compare where does

6:53

your lesion or target lesion fall in terms of SUV.

6:57

But again, it was developed for plain Octreotide scan.

6:59

There's also something called sink effect, uh, which

7:02

can result in a decrease in physiologic avidity.

7:04

This is most commonly seen in, um...

7:08

So if a patient has neuroendocrine tumor with numerous

7:11

metastases, for example, they could develop, um, with,

7:16

so the metastases will have high avidity, but the

7:18

liver parenchyma itself will be colder than expected.

7:21

So then you can't really use that colder than

7:24

expected liver parenchyma as your reference.

7:29

So just some important things to consider.

7:32

Here's, again, I'm showing you a maximum

7:35

intensity projection, whole body PET, or

7:38

skull-high PET image, um, of a normal subject.

7:42

And this is a patient with

7:44

metastatic, uh, neuroendocrine tumor.

7:47

This is the sink effect I was referring to.

7:49

So here you can see that, uh, in the right posterior

7:52

hepatic lobe, there's an intensely avid mass,

7:55

centrally necrotic, and you can see that the rest of

7:57

the liver looks actually quite cold for a Dotatate

8:00

PET, so lower than a normal liver would look like.

8:05

A little bit on diagnostic accuracy.

8:07

Um, 'cause we often get asked sort of how, what

8:10

is the sensitivity and specificity when it comes

8:13

to using Dotatate, um, for neuroendocrine tumors?

8:17

It's really excellent when, if you ask

8:20

the question, what's the accuracy for

8:22

detection of somatostatin receptor

8:23

2A, it really correlates directly with,

8:27

um, findings on, um, for example RT-PCR,

8:31

so kind of, um, expression analysis.

8:35

Um.

8:36

However, there's the caveat that not, there's

8:40

some degree of, even though most of these

8:41

tumors do overexpress SSTR2A, um, there's

8:45

some degree of variability, which is what

8:47

detracts a little bit from the sensitivity and

8:49

specificity and makes it slightly less than 100.

8:53

Um, and it's probably highest for the midgut

8:55

NET, but still pretty good for, uh, the others.

9:00

Um, relatively slightly lower for lung NET.

9:06

And this is from this paper if

9:07

you're interested in reviewing it.

9:11

Um, indications in this particular paper were,

9:14

um, predominantly for follow-up, um, staging and

9:18

restaging, and then recurrence evaluation.

9:23

So here they were also looking at, does it,

9:26

that's the other question I often get asked, uh,

9:28

how does Dotatate potentially change management?

9:32

And you can see that a fair number of,

9:34

um, cases, around 40 to 50%,

9:39

uh, they saw a change in management based

9:43

on the results of the Dotatate PET CT.

9:46

This is in a fairly large, um,

9:48

registry study with over 1,200 scans.

9:54

Um, as far as, um.

9:56

Implications for survival.

9:58

So in metastatic neuroendocrine tumor, in patients who

10:02

have bone mets, um, at diagnosis, survival is much

10:07

worse as compared to patients who do not have bone

10:10

metastasis, but rather soft tissue metastasis only.

10:14

And then unsurprisingly, it's, uh, the best for

10:17

patients who don't have metastatic disease.

10:19

Or who have localized disease.

10:21

So that's an important takeaway that, um, the

10:23

Dotatate, or any somatostatin receptor-targeted PET,

10:26

can help you, um, at kind of initial staging.

10:30

This question of bone metastases present or not.

10:34

This is with regards to the grades.

10:36

So of course, the higher the tumor

10:38

grade, the worse the survival.

10:40

Importantly, tumor grade does not necessarily

10:43

correlate with somatostatin receptor expression

10:45

and thus does not correlate with, um, SSTR

10:49

PET SUV. Limitations here, where this was

10:52

done retrospectively, and patients received

10:55

different types of therapy in this cohort.

10:59

So, as I just alluded to, as

11:01

far as correlation with grade.

11:03

So there's this grading of GI

11:05

neuroendocrine tumors based on Ki-67,

11:08

um, so proliferation index, and it's

11:11

basically low, intermediate, and high grade.

11:14

And essentially it does not correlate.

11:16

You can see that the higher

11:17

grades are actually expressed

11:20

um.

11:21

Less, um, SSTR and thus have lower

11:26

SUVs, but it's not a one-to-one.

11:27

So basically, you would expect, um,

11:32

somebody with a high-grade tumor to have, um, a

11:35

lower, um, SSTR-targeted PET SUV, uh, but you

11:40

can't really take this, um, at face value, so you,

11:44

you can't deduce from the SUV number what somebody's

11:48

tumor grade is, is essentially what I'm saying.

11:51

Um, but it's helpful to at least

11:53

gauge or get a sense of it.

11:55

So if it's very high, it might be

11:57

a more differentiated tumor, but

12:00

not, not sealed in stone.

12:04

So there's a weak, significant adverse correlation.

12:08

Um, what is the role of F-18 FDG

12:10

PET in, um, neuroendocrine tumors?

12:14

That's another question that often comes up.

12:17

Uh, basically, um, for example, based on this

12:20

study in over a hundred patients where they did

12:23

both, uh, Dotatate and FDG, um, in a subset of the

12:28

cohort, um, they found that it may be helpful in

12:32

patients with intermediate or high-grade NET.

12:35

So, uh, there's been some work done, um, looking at

12:38

that, like does it make sense to combine the two,

12:41

essentially the rough, ballpark idea here is that,

12:45

the more, the higher the tumor grade, the

12:48

lower, um, will be the differentiation,

12:52

and thus, FDG avidity will actually increase,

12:56

because the tumor becomes, sort of, the less

12:59

differentiated it is, the more aggressive it is.

13:02

So it helps a little bit with kind of

13:04

assessing what the tumor grade most likely

13:07

will be, but again, not sealed in stone.

13:12

Um.

13:13

As far as, uh, predictive value of, uh,

13:16

Dotatate PET, uh, for Lutetium Dotatate PRRT.

13:20

Um, so that's helpful to kind of see who

13:25

would be good candidates for the therapy.

13:28

So this is from the, um, NETTER-1 trial,

13:31

which was the landmark publication that

13:33

showed, um, utility of, uh, Lutetium Dotatate

13:37

PRRT for patients with, um, metastatic,

13:41

malignant neuroendocrine tumors, specifically midgut.

13:45

And that, uh, with Lutetium Dotatate,

13:47

they had much better progression-free

13:49

and overall survival compared to control.

13:53

So, um, as far as evaluating, um, who is

13:58

suitable for this therapy using Dotatate PET, in

14:01

um, this study referenced here, just recently

14:05

published in JNM, um, they looked at, um,

14:09

kind of baseline and interim Dotatate PET CT, and

14:13

how the, um, whether that was a predictor of

14:17

response, and in fact, higher, um, SUV values in

14:21

both absolute and ratio were predictors of response.

14:25

However, uh, the change in SUV after

14:29

treatment did not correlate with outcomes.

14:32

So the takeaway here is that, um, it is useful.

14:35

The Dotatate PET is very useful in assessing

14:38

tumor burden, so making the diagnosis, assessing

14:41

tumor burden, and predicting who will respond well

14:44

to treatment, um, but the change in the number

14:49

cannot necessarily be used to

14:52

assess the degree of response.

14:53

What this means is, as opposed to FDG, where

14:55

we really are looking for resolution of this

14:59

hypermetabolism, right, in the resolution of this high

15:02

FDG avidity, for example, in lymphoma post-therapy.

15:07

But here we're looking for:

15:09

Is the SUV significantly high at the

15:13

time of diagnosis? Then this patient is

15:15

a good candidate for Lutetium DOTATATE PRRT.

15:19

But then we can't necessarily draw conclusions

15:21

from the exact change in the SUV value.

15:29

And, uh, I'm going to show you now, uh, some

15:32

cases, and I, um, will just walk you through

15:35

them and you can, um, think a little bit about

15:38

what could the possible, uh, diagnosis be.

15:41

Okay.

15:41

So this is a 67-year-old woman with

15:43

clinically suspected neuroendocrine tumor.

15:45

Initial evaluation, uh, you can

15:48

see here I'm showing you, um, maximum

15:50

intensity projection image, or MIP image.

15:53

And it's similar to the one I showed you earlier

15:54

from the review paper as far as what a normal, um,

15:58

image in Dotatate should look like.

16:02

And, um, you can see the only physiologic

16:04

focus intracranially is the pituitary gland.

16:07

And then you have, again, the

16:08

spleen, liver, kidneys, adrenals.

16:11

Um, and then you see this focus of

16:13

avidity kind of in the, uh, mid, um,

16:18

retroperitoneum. It's kind of unclear from the MIP

16:21

image, of course, what it's supposed to be.

16:24

So then when we look at it, um, on cross-sectional

16:27

images, you see this focus of circumscribed

16:30

avid uptake, and I'm showing you here the low

16:33

dose, the unfused, um, PET-alone image with the

16:37

um, low-dose, corresponding low-dose CT image.

16:42

And essentially this is in the

16:45

uncinate process of the pancreas.

16:48

And we ended up doing an MRI.

16:51

Even though just from these images, you can

16:53

see that the, um, CT looks pretty reassuring.

16:57

There's no obvious abnormality seen

16:59

here, but just to be extra careful.

17:01

And because the patient did have, uh, some

17:03

clinical symptoms, uh, we did an MRI as well,

17:06

um, which showed no abnormality in the pancreas.

17:10

And so this is actually physiologic DOTATATE avidity

17:13

in the uncinate process, which is a common, um,

17:16

pitfall in, uh, Dotatate PET imaging.

17:18

So it's something important to remember

17:20

that you can see because of heterogeneous

17:22

distribution of somatostatin receptors.

17:24

So at the pancreas, you can have in a subset of

17:27

patients, um, this physiologic, um, avidity here,

17:32

which typically has no structural correlate at all.

17:36

Um, but sometimes it can be helpful

17:38

to confirm with MRI as well.

17:41

Okay, so another case, uh, this is

17:43

a 64-year-old woman with metastatic

17:46

neuroendocrine tumor, uh, appendiceal carcinoid

17:49

that was s/p right hemicolectomy.

17:51

Um, so 15 years after her initial diagnosis

17:55

and surgery, uh, she presented with,

17:58

um, liver and mesenteric recurrence.

18:01

Um, biopsy showed, uh, grade one.

18:04

So then she was on, uh, long-acting

18:07

octreotide, um, on Sandostatin for a few

18:10

years, but then developed rising tumor markers.

18:13

So now undergoes, uh, Dotatate PET CT for

18:16

restaging, and this is what her images look like.

18:19

So you can see, um, extensive, um, foci

18:25

of intense uptake both involving, uh, the

18:28

bones primarily as well as the liver.

18:30

And that's, uh, from that image I showed

18:32

you earlier with regard to the sink effect.

18:35

So you can see this large again, intensely avid,

18:38

centrally necrotic mass and the rest of the

18:41

liver looks pretty cold in comparison.

18:43

Again, extensive osseous metastasis, and

18:46

as previously mentioned, um, osseous

18:48

metastasis portend adverse prognosis.

18:53

Um, so the next step, this patient underwent,

18:55

uh, PRRT with, uh, Lutetium Dotatate.

19:00

This was, in fact, a metastatic recurrence,

19:02

as I'm sure you have gathered.

19:06

So this is what she looks like.

19:09

The top panel is this patient after, um, two cycles

19:14

of Lutetium Dotatate, uh, PRRT, um, where, um,

19:19

when, if you compare to the bottom panel, which is

19:22

the, um, initial evaluation I just showed you, um,

19:25

the images look very similar, and if you compare

19:28

the SUVs numerically, they're also quite similar.

19:32

So basically there is no

19:34

substantial change.

19:35

Now, this is after two cycles.

19:36

Typically, um, patients undergo four cycles

19:40

of treatment, and she had kind of a mid,

19:42

mid-treatment, uh, interim evaluation.

19:46

So no change in this case is a good thing.

19:50

We don't expect, again, just like with,

19:52

unlike with FDG, we don't expect, um, the

19:56

avidity to go away after Lutathera, but if

20:00

there's no new lesions, that's a good thing.

20:03

So stable disease.

20:06

So another case, uh, this is a 64-year-old

20:09

woman who presented with dysphonia, and I'm

20:11

showing you a, um, contrast-enhanced MR image.

20:15

Um, and you see here in the, uh, right sphenoid

20:19

sinus is a kind of hypoenhancing mass.

20:24

Um.

20:25

So think about what the

20:27

differential for this might be.

20:28

Uh, sinonasal mass.

20:31

Um, this was resected and this is what,

20:34

uh, her images looked like postoperatively.

20:36

Looked like gross total resection.

20:38

Of note, there was a little bit of, um, plaque-

20:42

like, uh, dural thickening here along the right,

20:45

um, jugular wall of the right cavernous sinus.

20:49

Um.

20:52

And so this was actually a case

20:54

of esthesioneuroblastoma.

20:57

And, um, she had gross total resection of

21:00

her esthesioneuroblastoma, of her, uh, primary tumor.

21:02

However, there was this additional small focus which

21:06

corresponded to this, which was not picked up on the

21:08

initial MRI, this asymmetric dural thickening.

21:13

And, um, this is favored to represent meningioma.

21:17

So her actual esthesioneuroblastoma was completely

21:19

resected and she had no metastatic disease.

21:22

Uh, but she had this, uh, small presumed

21:24

meningioma, which of course we can't be

21:26

100% sure without, um, sampling that tissue.

21:30

But this is not very amenable to

21:33

sampling because of the location.

21:35

But just based on, uh, long-term

21:37

follow-up, it has not changed.

21:45

Here's another case.

21:46

This is also an esthesioneuroblastoma patient.

21:49

Um, he was found to have a left nasal cavity

21:51

mass. After resection, it was, um, confirmed

21:53

to be esthesioneuroblastoma, Hyams grade 2 and Kadish D.

21:58

That's the grading and staging of esthesioneuroblastoma.

22:01

Um, he had, uh, positive, uh,

22:04

cervical nodes for metastasis.

22:06

Some of the nodes demonstrated

22:07

extranodal extension.

22:09

He underwent adjuvant radiotherapy to the neck, and

22:13

subsequently was followed with, um, serial imaging.

22:16

And so interestingly, this, uh, gentleman developed

22:21

a left, um, pararenal space mass,

22:24

shown here intensely Dotatate-avid, as well as this

22:28

uh, multifocal dural thickening with corresponding

22:32

Dotatate

22:33

avidity.

22:34

This is a Gallium-68 Dotatate PET

22:37

MR, and I'm showing you cross-sectional

22:39

images as well as the MIP image.

22:41

Uh, he also had a lesion in an anterior rib,

22:45

which was not apparent on, um, MRI alone.

22:48

Um, the only sequence it was apparent

22:50

on, which I'm not showing you here,

22:51

was the diffusion-weighted image.

22:54

Um, but otherwise it was very difficult

22:56

to see, but was intensely avid on DOTATATE.

23:00

And so, given this, uh, significant burden

23:03

of metastatic disease, we treated this

23:05

patient, uh, with Lutetium Dotatate PRRT.

23:11

Because, um, really there, there were no

23:13

other good treatment options available.

23:16

And so typically after Lutetium

23:21

Dotatate PRRT, um, we, as standard of care, we

23:24

only do the whole-body, uh, planar scintigraphy.

23:28

But because of, um, how unusual

23:31

this case is and the extensive disease

23:33

burden, we, um, also performed SPECT CT.

23:37

Um, so post-Lutathera SPECT CT.

23:40

Um, using Bremsstrahlung, um, from the Lutathera,

23:47

uh, to demonstrate that the, uh, PRRT agent

23:51

in fact went to those same areas, which were

23:54

also, uh, avid on the PET.

23:57

So this really confirms nicely your

24:00

kind of principle of theranostics.

24:02

So you use the PET agent for diagnostic

24:05

purposes and then you use a therapeutic

24:08

agent, um, that is a beta-minus emitter,

24:11

um, but otherwise has analogous structure to the

24:16

PET tracer, um, to actually treat your disease. So

24:19

you can see where the disease is, and then you can

24:22

treat it, and you know that it should work because

24:25

your, um, the lesions have shown avidity on the

24:28

PET. And this patient remains, uh, stable

24:32

as well after completing his Lutetium treatment.

24:40

Here's another case.

24:41

This is a 50-year-old woman with history

24:44

of, uh, glomus jugulare paraganglioma, posterior

24:47

stereotactic radiosurgery several years prior and

24:50

now, um, undergoing surveillance imaging.

24:55

And I'm just showing you this one, uh, set of coronal

24:58

images, um, post-contrast T1 and, uh, T2.

25:03

And you can see these, um, multiple

25:06

T2 hyperintense, um, mostly, but with some

25:10

flow voids in there, creating this kind of

25:12

salt-and-pepper appearance, uh, circumscribed

25:14

masses, including at the carotid bifurcation.

25:18

And they are also avidly enhancing, shown here.

25:22

And of course, uh, this looks very

25:23

suspicious for multiple paragangliomas.

25:26

Um, paragangliomas have very high expression

25:29

levels of SSTR2, so Dotatate can be used

25:32

to confirm the diagnosis in this case.

25:34

Um.

25:35

Oops.

25:36

Um, sorry.

25:36

In this case, you know, the MR appearance is

25:39

very classic for paraganglioma, and so we are

25:43

able to make the diagnosis based on MR alone.

25:46

But, uh, Dotatate is still very helpful because it

25:48

is important in patients with, um, paragangliomas to

25:52

know the extent of disease for treatment planning and

25:56

to know whether any additional paragangliomas are.

26:00

Uh, present elsewhere in the body

26:03

that we might not be aware of.

26:04

And for example, in this particular patient, not only

26:08

did she have bilateral, um, glomus jugulare paragangliomas,

26:12

uh, glomus vagale, which you can see here, um, as

26:17

well as, um, carotid body paragangliomas.

26:22

She also had, um.

26:24

Paraganglioma that would otherwise not have

26:27

been detected based on, um, anatomic imaging

26:30

alone, um, kind of below the aortic arch.

26:33

So presumed glomus aorticum paraganglioma.

26:37

So this was somebody who had, um, you know, a

26:40

predilection for multiple paragangliomas, had some

26:42

family history, and, um, with Dotatate PET, we were

26:45

able to, um, appropriately delineate disease extent.

26:51

Here's another patient, a 40-year-old woman,

26:54

history of a right carotid body paraganglioma,

26:57

resected 10 years prior, now with progressive

27:00

dysphagia to solids over the past year.

27:04

So, uh, this patient had a—this is, I'm

27:07

showing you T1 pre-contrast and, uh,

27:10

fat-accelerated post-contrast images.

27:13

And then, uh, the bottom panel is FDG PET.

27:16

Initially they weren't sure, I guess, what it was

27:19

or did not have the records that she previously had.

27:21

The history of paraganglioma.

27:24

So they started with, um, MRI followed by

27:27

FDG PET. The MRI shows this, um, mass in the

27:31

parapharyngeal space that is avidly enhancing,

27:35

um, not showing you the T2, but it also

27:38

had the kind of typical appearance with, um,

27:42

T2 hyperintensity and flow voids.

27:45

Um, it was also intensely FDG-avid, and in

27:48

fact, the extent of FDG avidity, um, exceeded

27:52

what you can, uh, delineate well on the MRI.

27:54

So the mass kind of, um, extended,

27:57

um, inferiorly and laterally.

28:00

Um, so.

28:03

Given that this was, um, given, given this

28:06

appearance, the location, the right carotid

28:08

space, um, very high SUV, and the fact that

28:12

she, on this, uh, image, you can't see it, but

28:14

she had numerous additional FDG-avid lesions.

28:17

Um, this was concerning for metastatic process.

28:23

And initially the consideration was

28:25

not necessarily metastatic paraganglioma,

28:27

given how rare that entity is.

28:30

So they tried doing a biopsy.

28:33

Oh, and here is the CT, the PET/CT FDG PET/CT

28:36

images, and you can see numerous lesions not

28:39

readily apparent on CT, but intensely avid on

28:42

FDG PET throughout the cervical and thoracic spine.

28:47

And so the CT-guided biopsy was non-diagnostic,

28:51

which is not that uncommon with paraganglioma,

28:52

because of how vascular this tumor is.

28:55

So Dotatate PET/MRI, um, which we subsequently

28:58

performed, demonstrated intense Dotatate

29:00

avidity of all previously visualized lesions.

29:04

So now that we have established that this is in fact,

29:07

um, metastatic paraganglioma, um, we recommended,

29:11

uh, Lutetium Dotatate PRRT, which this

29:16

patient underwent, and she remains, uh, stable.

29:19

This is, uh, her.

29:21

PET MIP image, uh, prior to PRRT, and

29:25

this six months post completion of

29:27

PRRT, so she remains stable as well.

29:32

Uh, here's another case.

29:34

Uh, this is a 54-year-old man with a remote history

29:37

of pheochromocytoma of the right adrenal gland,

29:40

post-resection, now with rising plasma metanephrine.

29:44

And you can see that he has this focus, um,

29:47

of intense avidity in the, um, right retroperitoneum,

29:53

but importantly, uh, so here I'm showing you

29:55

the fused, uh, images on panel B and

30:00

panel C is the corresponding, uh, CT image.

30:04

And then, uh, panel D and E are actually

30:08

slices, axial slices from a little bit higher.

30:10

So this is where you see the surgical clips in the

30:13

right retroperitoneum where he had his original

30:16

tumor that was resected, and that whole area is

30:19

photopenic, meaning there is no local recurrence.

30:22

However, um, further down there is this focus,

30:26

and this was—I'm not showing you the FDG images,

30:28

but this was actually missed on the FDG PET.

30:31

Um.

30:32

Because it had very similar FDG to normal

30:35

liver parenchyma, but it is intensely avid.

30:38

Um, a focus of intensely avid soft

30:41

tissue along the right posterior hepatic surface.

30:45

And this was, um, pathology-proven

30:48

recurrent, um, malignant pheochromocytoma.

30:55

Okay, and now I'm going to show you

30:57

a couple more neuro-focused cases.

31:00

And that, since that is my favorite thing to talk

31:02

about, this is a 53-year-old man with meningioma.

31:05

So you can see that this mass has

31:08

a fairly typical appearance for meningioma.

31:11

It's avidly enhancing, extra-axial, um, dural-based,

31:15

here along the falx, the left parietal falcine location.

31:20

Uh, this was resected and, uh, post resection,

31:23

he developed this, uh, nodularity

31:25

here along the posterior falx, um,

31:28

near the cr—near the resection site.

31:31

Uh, Dotatate PET/MRI demonstrated

31:35

clearly the extent of, um, recurrent tumor.

31:38

You can see these two foci.

31:40

So now, instead of irradiating the entire

31:43

resection cavity, um, we were actually able

31:46

to plan his, um, SRS just targeting those

31:50

areas that demonstrated intense avidity.

31:56

And this is what his, um, radiation oncology

32:00

plan—his treatment plan—would look like

32:02

based on the entire resection cavity.

32:04

Um, so standard of care MRI.

32:07

Um, however, if you use the Dotatate

32:10

PET/MRI, which we did in this case,

32:12

um, his PTV would be reduced tenfold.

32:17

Here's another example.

32:18

This is a 38-year-old woman,

32:20

um, who presented with seizure, uh, no prior

32:23

medical history, and this is her preoperative MRI.

32:26

You can see that, uh, while somewhat similar to

32:28

the previous case, this mass looks a little bit

32:31

more heterogeneous in the enhancement pattern.

32:33

There's also pronounced hyperostosis,

32:35

um, of the frontal calvarium.

32:37

Um, there's central areas of hypoenhancement.

32:40

There was also invasion, not really shown well here,

32:43

but there was invasion of the superior sagittal sinus.

32:47

And which is why, um, you know, the neurosurgeon

32:50

wasn't able to resect the entire tumor.

32:53

This is what her post-op MRI looked like.

32:56

So it was definitely, um, mostly, uh, they were able

33:01

to resect the vast majority of the tumor.

33:05

Um.

33:06

It was gross total in terms of the operative report.

33:10

Although given the location, there

33:12

was a high risk that some microscopic

33:14

disease may have been left behind.

33:17

So they discussed, uh—or we discussed in

33:19

tumor board—the options, and as far as

33:21

radiation of the resection cavity or just

33:24

following prospectively, uh, she wanted to delay

33:28

uh, radiation.

33:29

So it was followed.

33:31

And then subsequently she developed this

33:32

increasing area of enhancement in the resection

33:35

cavity, which was concerning for recurrent tumor.

33:38

You can probably best see it here on the coronal

33:41

images, and you can see that the proximity

33:44

to the superior sagittal sinus, um, places her at high risk for recurrence.

33:52

And so Dotatate PET/MRI demonstrated well the

33:56

extent of residual/recurrent, um, meningioma.

34:01

This was at five months postoperatively.

34:03

And so again, we were able to plan her radiation

34:06

treatment together with her, uh, radiation

34:09

oncology colleagues, um, on the basis of these

34:12

images, which helped, um, deliver higher dose

34:16

of radiation to a smaller area and spare, um.

34:21

Adverse effects of irradiating uninvolved

34:25

tissues, especially uninvolved brain parenchyma.

34:28

So this is what her plan would have

34:30

looked like based on, uh, MRI alone.

34:34

And this is what her actual plan

34:36

looked like based on the PET/MRI.

34:40

Uh, this is just to summarize, uh, the findings.

34:43

Uh, pre-radiosurgery images A to F, and then

34:46

corresponding images G to L are post-radiosurgery,

34:50

um.

34:51

And this is her most recent follow-up.

34:58

And, uh, she remains, um, stable as far as there's no,

35:02

uh, evidence of persistent or recurrent meningioma.

35:06

And she had, um, as an adverse

35:08

effect of the radiation,

35:09

she had some, uh, alopecia, um, but

35:12

now, um, that has fully resolved.

35:17

And then I have one more case, uh, to demonstrate

35:19

that, um, somatostatin receptor-targeted PET in

35:23

the brain can also be helpful for kind of problem

35:26

solving when you're not 100% sure what's going on.

35:30

So this is a 50-year-old man with history

35:32

of WHO grade three anaplastic astrocytoma,

35:35

who underwent, uh, surgery and radiotherapy.

35:40

Was considered, um, gross total

35:43

resection, no residual or recurrent tumor.

35:46

Um, and now presents with headaches.

35:48

This is his resection cavity in

35:50

the left posterior temporal lobe.

35:53

And you can see there's—I'm not showing you

35:54

the T2 images, which would be important, uh,

35:57

to look for, um, expansile, T2 hyperintense

36:00

mass, which—but were negative for that.

36:04

Uh, you can see no significant enhancement,

36:06

uh, except for a little bit of curvilinear

36:08

enhancement here, posterolaterally.

36:10

So all of that looks like, uh, there is no

36:13

residual or recurrent disease at the resection bed.

36:16

However, he had this, which was

36:19

new, um, from prior studies.

36:21

Um, so this new dural-based, avidly enhancing

36:25

nodule here and an additional, so kind

36:28

of along anterior left parietal falcine.

36:32

And then an additional, um, apparently dural-

36:35

based, uh, enhancing nodule, not quite as

36:38

avidly enhancing, but still, um, kind of, uh,

36:41

in the, uh, right cerebellopontine angle cistern.

36:47

And so based on this appearance, uh,

36:50

the initial thinking was, um, when we

36:53

discussed him in tumor board, well maybe he

36:56

developed, um, meningiomas related to the

37:00

radiotherapy. It's considerable.

37:04

And so we performed, uh, Dotatate in

37:07

this case, PET/CT, um, to confirm that.

37:12

So we were hoping to see that these tumors would

37:14

be intensely Dotatate avid, which would, uh,

37:17

reassure us with regards to the, um, etiology.

37:23

However, um, what you can see here is that

37:26

these tumors only had very low-level avidity.

37:30

So this is again, uh, intense

37:32

avidity found physiologically in the sellar

37:35

from pituitary, normal pituitary tissue.

37:37

You can see that his whole resection cavity

37:39

is pretty much cold, as would be expected.

37:42

There's some, you know, encephalomalacia,

37:44

and gliosis with no significant associated

37:46

avidity, and now his, um, two lesions

37:51

demonstrate, again, very low-level avidity.

37:55

So SUV was maybe between three

37:57

and four, which is quite low.

38:00

Um, and so based on this, we couldn't definitively

38:04

confirm that these are meningiomas and.

38:09

On subsequent imaging, they actually demonstrated

38:12

enlargement in a relatively short interval.

38:14

So this patient ended up undergoing resection of

38:17

this falcine lesion, and the pathology

38:21

demonstrated, um, an anaplastic astrocytoma.

38:25

So this is a fairly unusual but,

38:29

um, possible outcome where the

38:33

astrocytoma, um, somebody with astrocytoma

38:36

developed a dural-based, uh, recurrence.

38:40

So it's, uh, the reason I'm showing this case

38:42

is because it's a good example of how, um,

38:47

Dotatate can be helpful with problem solving.

38:50

We've definitely seen cases like that.

38:52

There are always textbook appearances of

38:55

things like meningioma, paraganglioma.

38:57

They all have textbook MR findings.

39:00

However, if, for example, you have a mass in

39:04

the neck that has some features that make it,

39:09

um, more typical for schwannoma, but then

39:12

the location and the patient's clinical

39:15

presentation suggests possible paraganglioma.

39:18

That's where, um, Dotatate can also be helpful.

39:22

And so this is an example where a

39:23

negative Dotatate, uh, guided management, um.

39:27

In the direction of, uh, obtaining

39:30

tissue for diagnosis and confirming the

39:33

diagnosis as not meningioma, but rather

39:36

anaplastic astrocytoma in this case.

39:39

So it's just as far as, um, research, uh, going

39:43

on at this institution and other institutions,

39:46

uh, with regard to Dotatate-guided, um, or

39:49

Dotatate-based, um, PET imaging and, uh,

39:54

PRRT therapy.

39:55

So DOMINO-START is our trial at Cornell for,

39:58

uh, Dotatate PET/MRI in, uh, somatostatin in

40:02

meningioma and other somatostatin receptor-

40:05

positive tumors of the brain, head, and neck.

40:09

Um, and that's, uh, nearing, uh, filling

40:13

enrollment, um, pretty soon.

40:17

Um, so Lutathera or Lutetium Dotatate in Mening-

40:22

is a clinical trial that is, uh, being run

40:26

by our colleagues at NYU, and um, we are, uh,

40:30

working on activating it at Cornell as well.

40:33

So meningioma—this is for patients with

40:35

meningioma who have, uh, progressed through

40:38

conventional therapy, being surgery and radiation.

40:42

Um, we're also looking at comparing Dotatate to Dotatoc.

40:46

Um, seeing that Dotatoc is, um,

40:51

potentially, uh, cost saving and, um, maybe

40:57

equivalent with regards to, um, delineating, um,

41:01

meningioma extent based on publications mostly, um,

41:05

from colleagues in Europe, Munich in particular.

41:09

Um.

41:10

Another, um, project currently in preparation is

41:15

using, uh, Dotatate for intraoperative guidance.

41:18

This is something where, um.

41:21

Compounds with longer half-life

41:22

would particularly be advantageous.

41:25

And, uh, recently approved, uh, Copper-64 Dotatate,

41:28

which I haven't gone into because we are

41:31

just starting to image patients with Copper Dotatate.

41:35

Um, but the half-life is longer.

41:37

Um, so instead of the 68 minutes from the

41:40

Gallium compound, the half-life here is, um.

41:44

Closer to 18 hours.

41:46

So it would be conceivable to inject somebody with

41:49

Copper Dotatate and then use, um, an intraoperative

41:53

gamma probe to guide, uh, extent of tumor delineation.

41:59

So this is in progress, actually.

42:01

Uh, we're also working on dynamic PET imaging

42:03

for, um, optimization of our existing

42:07

PET protocol and evaluating utility of

42:10

dynamic parametric mapping for treatment

42:13

planning and response assessment.

42:16

And, uh, we also recently completed a

42:18

cost-effectiveness analysis, given the

42:21

higher upfront cost of doing Dotatate PET

42:23

compared to, uh, you know, standard-of-care

42:26

MRI, um, which shows that there's definitely

42:30

um, an improvement in, uh, both the

42:33

effectiveness and decrease in the cost.

42:36

Um, so better quality-adjusted

42:38

life years and lower costs.

42:41

Um, so hopefully this will find its way into

42:45

wider clinical practice in the near future.

42:49

I think this is all I have, uh, as far as cases.

42:52

I want to thank my colleagues at Cornell in the

42:56

radiology department and our collaborators in other

42:58

departments, and of course our patients and their

43:02

families, and I'd be happy to take any questions.

43:06

Thank you very much.

43:08

Sure.

43:11

We'll take a look.

43:12

Okay, so great question.

43:13

Does anaplastic astrocytoma have SSTR2A?

43:17

So in that case I showed you it was not zero, right?

43:20

So, um, there is—

43:23

low-level avid or mild avidity. It was

43:26

kind of borderline with what we see as,

43:29

um, significant avidity for meningiomas.

43:33

Um, which based on our own experience with our cohort,

43:37

um, where we've conducted, uh, threshold analysis, it

43:41

looks like if the SUV of the meningioma is three times

43:46

or higher than that of the superior sagittal sinus,

43:50

which, um, we are using as a sort of, uh,

43:54

blood pool reference.

43:56

Um, so if it's greater than threefold higher

43:59

than that, that's considered a positive.

44:01

And so in this particular case, the anaplastic

44:03

astrocytoma had a kind of borderline—

44:07

around three times higher or slightly less.

44:10

Than the superior sagittal sinus.

44:12

And that's what made us concerned

44:13

that this is not meningioma.

44:15

Um, I know that there are some studies published,

44:18

uh, with, uh, small case numbers, but, uh, where

44:22

they used, uh, Lutetium Dotatate to treat, um, uh—

44:26

high-grade gliomas.

44:28

So, um, I think the numbers are too small to

44:32

be able to gauge whether this is something

44:34

that could be implemented more widely.

44:36

There's definitely some degree of SSTR2A

44:39

expression, but it's by nowhere near as high

44:42

as, for example, meningiomas or paragangliomas.

44:46

So I don't think it's, um, the best, um, biomarker.

44:55

Why is Dotatate sensitivity higher

44:57

in intermediate-grade tumors?

45:00

Um, I'm not sure that it can really

45:02

be, uh, generalized in that way.

45:05

I think it's, um, the, the reason it's—

45:11

higher in—basically you can think of it

45:13

as Dotatate correlates nearly one to one

45:16

with a gene expression of SSTR2A gene

45:20

and protein expression of SSTR2A.

45:23

So if something overexpresses SSTR2A, it'll have,

45:25

um, high Dotatate avidity.

45:29

So depending on your case numbers, you

45:33

will have some fluctuations in sensitivity

45:36

and specificity, uh, when using

45:40

Dotatate SUV, uh, thresholds.

45:43

But, um, in general, I would say it will be lower

45:49

in high grades because the avidity goes down.

45:52

So if your numbers go down, you're

45:55

more likely to lose some sensitivity.

46:02

Alright, well I invite any other attendees.

46:03

If you have any questions, please

46:05

direct them to the Q and A window.

46:07

It looks like we do have

46:09

another one that just came in.

46:11

How interesting—do you use Gallium-68

46:13

somatostatin analogs for insulinoma in infants?

46:16

Um, I have not personally, um,

46:18

seen such a case, but, um, it.

46:22

Should work.

46:23

We have, um, had only one instance where

46:26

a child, um, there was a concern for a glomus

46:29

tympanicum in a young child, I think a 2-year-old.

46:33

So we do have a pediatric imaging protocol and it

46:36

is approved for pediatric, uh, PET imaging, PET CT,

46:42

and PET/MRI. Uh, you just use weight-based dosing.

46:45

And, um, so it definitely is conceivable, but,

46:49

uh, I have not personally come across, um, that

46:53

particular diagnosis or suspected diagnosis.

46:56

We have used it in that child, um, where the

46:59

question was, um, glomus tympanicum, and, uh, the questioned

47:04

lesion was completely negative on the Dotatate and

47:07

ended up resolving and was probably inflammatory.

47:11

So definitely it can be applied

47:13

to the pediatric population.

47:18

I see that another question came through

47:20

the—just saw that come through too.

47:22

Yeah.

47:23

Yeah.

47:23

So, um, someone asked, how do

47:25

you assess response to Lutathera?

47:27

So, uh, that's a great question.

47:28

So, as we discussed, uh, Dotatate PET is

47:33

great for determining whether somebody

47:35

is a good candidate for Lutathera.

47:38

Uh, but it's challenging to gauge from

47:41

just a change in SUV—you basically cannot

47:43

use it for direct, uh, response assessment.

47:46

I think the best thing you can

47:47

do is to look for, um, any—

47:50

new Dotatate-avid lesions, which

47:52

would be concerning for progression.

47:54

And any, um, marked increase in both

47:58

avidity and size on, uh, the CT, uh, would

48:02

also be worrisome of existing lesions.

48:04

So the lack of, um, both of those and

48:08

ideally decrease—but we can't, uh,

48:11

quantify exactly how much of a decrease

48:16

would we be happy with?

48:17

So basically, when somebody post-

48:20

Lutathera has stable disease, that's considered good,

48:26

and the lack of progression.

48:29

Alright, well I think that

48:30

might be it for the questions.

48:33

Um, I'll keep an eye on the Q and A, but

48:36

uh, as we bring this to a close, I want

48:38

to thank Dr. Ivandize for this lecture today.

48:42

And thanks to all of you for

48:43

participating in our noon conference.

48:45

A reminder that this conference will be

48:46

available on demand on mrionline.com in

48:50

addition to all previous noon conferences.

48:52

Be sure to join us again on Friday for a

48:54

lecture from Dr. Rajat Jain—that will

48:57

be prerecorded, but it will be on the

48:58

brainstem, cerebellum, hydrology, and imaging.

49:02

You can register for that at mrionline.com and follow

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us on social media at MRI Online for updates

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and reminders on upcoming noon conferences.

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Thanks again and have a great day.