0:01

So moving now to part four,

0:03

and this is our radiopharmaceuticals

0:05

and again, we're talking about PSMA ligand PET

0:08

and just our definition.

0:09

So the use of PSMA ligand, that's the technical term

0:12

as our radiopharmaceuticals are PSMA ligands.

0:14

The PSMA itself is on the cell surface in the body.

0:18

So we are modeling PSMA expression

0:21

and we've mentioned that there are several

0:23

PSMA ligands available.

0:24

Um, commonly gallium 68 P SMMA 11

0:27

or Gallium 68 PSA as I'll be referring to it

0:30

or F 18 FDCF pile or PSR.

0:34

And these are both common in practice,

0:36

but when would you choose, um, gallium 68 PSMA

0:39

or PSR, um, in your practice?

0:42

Um, they do have similar biodistribution

0:44

and it is easy to compare these images

0:47

to each other in terms of side by side studies.

0:49

Gallium 68 has been found to have higher activity

0:52

through the urinary tract spleen and saliva glands,

0:54

but I've noticed that the splenic uptake can be variable

0:57

and often the urinary tract, you know,

0:58

you will see quite intense uptake regardless

1:00

of the tracer you use.

1:02

The tracer uptake is also pretty similar in liver.

1:05

One of the advantages of gallium 68 PSMA

1:07

and as we've mentioned, has the ability

1:09

to form a theranostic pair with LUTETIUM 1 77.

1:12

So we can swap out the gallium 68 PSMA

1:15

for lutetium 1 77 for targeted therapy.

1:18

Um, in terms of cost, you know,

1:20

that would be a consideration of whether

1:21

or not the place that you work has access

1:25

to a gallium generator, um,

1:27

and train staff to be able to use that generator

1:30

and produce the tracer and then label it with PSMA.

1:34

So gallium 68, it's a positron emitter, um,

1:36

because we're looking at PET scans.

1:38

Positron emission tomography has a half-life of 68 minutes,

1:41

which makes it ideal for diagnostic imaging.

1:43

Um, and it's created from a generator which can be loused in

1:46

hot labs or the radio pharmacy on site at the pet suite

1:50

in these generators.

1:51

Germanium 68 decays to gallium 68,

1:53

which is a positron emitter.

1:55

And as we mentioned gallium 68, 1

1:57

of the advantages is its application as a theranostic pair

2:00

with LUTETIUM 1 77.

2:02

So by imaging pre theranostic treatment with gallium 68,

2:05

we can determine the suitability.

2:07

And this is an example of

2:08

what a gallium generator may look like.

2:12

Flu in 18 is a very common radiopharmaceutical

2:15

for positron emission tomography.

2:17

Um, FDG PET has been the workhorse

2:19

of clinical positron emission tomography

2:21

for such a long time, um, as metabolic activity is something

2:24

that we really look for in a lot of malignancies,

2:27

hematological malignancies, lung cancer, bowel cancer, um,

2:30

gynecological cancers.

2:32

In terms of, um, its use in PSMA,

2:34

it's not the only, um, horse in the race.

2:37

Um, it's a positron emitter of course.

2:38

Um, as we are imaging with PET scans with a half-life

2:41

of 110 minutes, also making it ideal for,

2:44

um, clinical practice.

2:45

Um, these traces are delivered to site

2:47

and they're made on a cyclotron such as this, which is one

2:49

that's in the National Imaging facility in Australia.

2:54

So what do they look by side by side?

2:56

Um, so here's a Gallium 68 PSA and an F 18

2:58

PSR scan. This

2:59

is the same patient

3:01

who had two scans in two different institutions,

3:03

so we've put them side by side, so we can see

3:05

that if we look at the spleen on Gallium 68 PS MA,

3:09

their spleen is a bit warmer and hotter than the PSR pet,

3:12

but on PSR splenic uptake can be variable.

3:16

Um, also we kind of noticed that the ganglia seemed

3:18

to be popping out a little bit more on PSMA,

3:20

but that also can be variable between the two patients.

3:25

And interestingly, we'll just come back to this one.

3:27

You can see that there is uptake

3:29

below the bladder corresponding

3:30

to the prostate primary tumor.

3:31

However, it's not seen on this scan and that's

3:34

because the patient has undergone interval treatment

3:38

on a similar scan.

3:39

This is gallium 68 PSA versus PSR.

3:41

And the spleen you'll notice is hot on both of the scans.

3:46

Um, but you'll also notice that the, um,

3:48

auxiliary lymph nodes are a little bit more conspicuous.

3:50

Um, so inflammatory uptake was a little bit more conspicuous

3:52

on PSMA PET as well.

3:55

And you will notice that yes,

3:56

there was the hot primary on the baseline study

3:59

and this patient has undergone interval prostatectomy

4:02

and that accounts for the difference

4:03

that you see down in the bladder and in the pelvis.

4:06

So we're going to just close out this section just

4:08

by comparing PSMA PET CT and FDG PET ct.

4:11

And just because FDG isn't as sensitive in a lot

4:14

of prostate cancer patients does not mean

4:16

that there aren't clinical applications for it.

4:19

PSMA is great for that well differentiated prostate cancer

4:21

where there is upregulation of PSMA and FDG is better

4:25

and more sensitive for dedifferentiated disease.

4:27

So where the cells have lost their characteristics,

4:29

they're no longer upregulating PSMA on their cell surface.

4:33

It's really useful in the detection

4:34

of dedifferentiated disease,

4:36

but there's also a bit of a role for detection

4:37

of incidental findings as well.

4:40

So in this case, this patient actually has, um, paired PSMA

4:44

and FDG studies that all performed

4:45

in close proximity to each other.

4:47

Because on the PSMA study, we did find

4:49

that there was increased uptake in the prostate,

4:51

which was essentially FDG negative,

4:53

but there was some clinically significant incidental

4:55

findings including this lung lesion,

4:59

which was FDG avid, um, and mildly PSMA avid.

5:03

And then when we did the FDG,

5:05

there was further incidental findings of a bowel primary,

5:09

which was PSMA negative, but intensely FDG avid.

5:12

Um, so this was an interest in case showing the different

5:14

malignancies in a patient

5:17

with known metastatic prostate cancer and advanced disease.

5:21

This patient had skeletal and hepatic metastasis,

5:24

and interestingly, the skeletal metastasis is P SM a avid,

5:28

but not very FDG avid,

5:30

whereas this liver metastasis is very hypermetabolic

5:33

or FDG avid,

5:35

but essentially PSMA negative reflecting a site

5:38

of d differentiated disease that could be targeted

5:40

with a different therapy.