0:00

We're now going to move on to the third part,

0:02

which is going to be looking at the physiology

0:04

and pharmacology of PSMA pet.

0:07

And as we saw in the prior section, PSMA stands

0:11

for prostate specific membrane antigen

0:13

and it is a transmembrane type two glycoprotein.

0:16

There's physiological expression in many tissues

0:18

around the body, including sali glands, liver, spleen,

0:21

bowel, and renal excretion.

0:23

But this particular antigen is upregulated in well

0:26

differentiated prostate cancer cells.

0:29

In about 95% of patients, they will have PSMA AVID

0:33

or upregulation of PSMA tracer to allow it to be seen

0:36

as a hotspot on imaging.

0:39

And what does this kind of look like?

0:41

So we've got a short animation.

0:42

The PSMA ligands are seen in blue upregulated

0:45

in prostate cancer cells.

0:47

So when we inject the radiopharmaceuticals, so

0:49

that's the PSMA ligand in orange with a radioactive tag,

0:52

it is drawn into the cells

0:54

and then shoots out a gamma photon.

0:57

Um, the gamma photon isn't directly from the decay

1:00

of the positron emitter,

1:01

however, it's the byproduct of an annihilation reaction.

1:04

And this is the basis of PET scans.

1:06

The agent decays Gallium 68,

1:08

fluorine 18 sends off a positron, which is anti-matter.

1:11

It meets an electron.

1:12

They annihilate each other

1:14

and this annihilation reaction sends out two gamma photons

1:18

at 511 KEV at 180 degrees to each other.

1:22

These are called coincidence photons.

1:25

And if this annihilation reaction happens while the

1:27

patient's in the scanner, these two photons are shot out

1:29

along a line and then the PET camera will detect these

1:33

coincidence photons and then assume

1:35

that the annihilation reaction has happened

1:37

somewhere along that line.

1:39

By getting millions and millions of these reactions,

1:41

the PET scanner will build up an image

1:43

and a three dimensional representation of the distribution

1:48

of the radiopharmaceutical within the patient.

1:52

So as we alluded to the bio distribution of PSMA

1:55

and that this goes for all PSMA agents, is

1:58

that there is urinary excretion

2:00

and there is physiological uptake in some

2:02

extra prostatic tissues.

2:04

And so what does this normal distribution look like?

2:07

Here is a rotating map, then our MI projection showing

2:10

that there's uptake in sili and lacrimal glands, liver

2:13

and spleen, um, and bowel,

2:16

and then physiological excretion by the kidneys.

2:18

So we'll see hot, um, or very avid kidneys, ureters

2:22

and then excretion into the bladder.

2:26

And what does that look like in cross-sectional?

2:28

So this is a fused image. We'll be seeing a lot

2:30

of these in the upcoming modules when we get

2:32

to the scrollable cases, looking through.

2:34

So SIV glands, there's increased uptake

2:37

and then a lot through the parotid glands

2:40

and the submandibular glands.

2:41

So saliva glands all through the head

2:43

and neck will have intense uptake

2:44

because they have PSMA, um, antigen expression.

2:48

So coming down a little bit

2:49

of uptake in the thyroid, that's normal.

2:52

And then also there's a little structure just here at the

2:54

thoracic inlet, which I'll just draw your attention

2:56

to these tiny little dots.

2:59

These are ganglia

3:00

and we'll look at these in a little bit more detail.

3:02

Very common to see at the thoracic inlet

3:04

with the stellate ganglia.

3:06

The upper abdomen is the celiac ganglia

3:08

and also in the presacral space.

3:09

As our scanners are now picking up smaller

3:11

and smaller structures, a little bit

3:13

of uptake in the esophagus can be normal, um, as well

3:16

as some mild uptake in mediastinal lymph nodes.

3:18

It's often reactive or inflammatory.

3:20

Liver and spleen will have variable uptake,

3:23

often quite intense, and you've gotta adjust your parameters

3:25

when you're reading the studies for this one

3:27

of our celiac ganglias coming through.

3:29

And then the kidneys with a lot of tracer excretion

3:31

with our hot ureters side by side coming all the way down

3:36

into the bladder.

3:38

And this is where we expect

3:39

to see a tracer uptake in these patients.

3:41

And this patient has had a prostatectomy it looks like.

3:45

Um, but we also do expect to see, um,

3:47

heterogeneous tracer uptake in normal prostate tissue

3:50

because there of course is going

3:51

to be some PSMA expression in these tissues.

3:54

We'll have a look at some more normal studies in the

3:56

upcoming modules.