0:00

So to round out our presentations, we are going

0:02

to have a brief stop at Theranostics.

0:05

And Theranostics is one of the most exciting things

0:07

to be emerging in prostate cancer

0:09

treatment over the last decade.

0:11

And it is really, truly entwined

0:13

with Gallium 68 PSMA PET ct as well as when we swap out

0:18

that gallium, as we've heard

0:19

before, we can replace it with LUTETIUM 1 77,

0:22

which is a beta emitter

0:24

and that can deliver targeted radiotherapy

0:26

to tissues affected

0:28

by a well-differentiated prostate cancer.

0:30

So just to kind of briefly go through this,

0:33

and this is more just a bit

0:34

of a taster if you are interested, I do encourage you

0:36

to become more involved and read more widely on theranostics

0:40

or get involved if you have the program at your hospital.

0:44

So theranostics is a definition, it's the combination

0:47

of therapy and diagnostics.

0:48

So we're using, um, the same pharmaceutical

0:51

or the same ligand and swapping out the radioactive isotope

0:55

and we are able to target specific organs and tissues

0:58

and that's based on surface markers or receptors.

1:00

There's also lutetium dotatate therapy

1:03

for somatostatin receptor expressing well differentiated

1:06

neuroendocrine tumors as well.

1:08

And then we use that diagnostic imaging component

1:10

and the PET scan to confirm the target

1:12

and the suitability for therapy.

1:14

And then we deliver the targeted radiotherapy

1:16

at that cellular level.

1:17

There's conversations about whether these therapies are

1:19

palliative versus curative,

1:21

and at this stage they're primarily used in the palliative

1:24

setting for life prolongation

1:25

and for gaining improved quality of life

1:28

for these men who are affected.

1:29

In terms of results, it's variable.

1:31

Um, some men have really excellent responses,

1:33

some don't respond well at all.

1:35

Um, but for a lot of men

1:37

who have met well differentiated metastatic prostate cancer,

1:40

these therapies are really making a huge difference.

1:44

So what does it look like?

1:45

And we've brought back our animation about, um,

1:47

targeting the PSMA antigen, which we see here in blue

1:51

and we'll just get that running.

1:52

So it is upregulated in prostate cancer cells coming in

1:56

with our ligand

1:58

and our um, radio tracer, which is then taken into the cell.

2:03

And instead of kind of shooting out that gamma photon

2:06

or that positron, which then gives the annihilation

2:08

reaction, gives us the gamma photon, we have

2:10

a tracer in there which is in the cell

2:13

and it's delivering beta therapy, so electrons

2:17

and that electron interacts with the DNA

2:20

to cause DNA damage.

2:21

And if we can get double stranded breaks, then it means

2:24

that these cell repair mechanisms

2:26

of the prostate cancer cells are overwhelmed

2:29

and then they undergo apoptosis.

2:32

And that's what we like to see.

2:33

And so, you know, the half life

2:35

of lutetium is, you know, days.

2:37

And so over those days we can deliver targeted radiotherapy

2:40

and hopefully eventually end up

2:42

with cell death in these cancer cells.

2:46

So taking the protocol of the therapy trial

2:49

patients are in our institution,

2:50

we tend to follow this protocol.

2:51

They're given an intravenous infusion of LUTETIUM 1 77 PSMA

2:56

with six week breaks in between, the number

2:59

of treatments given is patient dependent

3:01

and the dose is approximately 8.5 giga.

3:04

Um, and then reducing by half a giga each cycle.

3:07

And then they undergo post therapy imaging at 24 hours.

3:10

Unfortunately with theranostics,

3:12

because as we know from our tracer distribution

3:15

and where there are some normal physiological structures

3:19

which do have PSMA like and uptake, including sali glands

3:22

and kidneys, we do need to be careful of side effects.

3:25

Um, and so dry eyes and dry mouth,

3:27

so dry eyes from the lacrimal glands dry mouth from

3:29

targeting the saliva glands is a potential side effect

3:32

of this treatment in addition to fatigue, pain

3:35

and nausea and vomiting.

3:38

So this is a nice, um,

3:39

case from the literature showing gallium 68 PSMA uptake.

3:43

And this is a patient with widespread disease,

3:45

predominantly skeletal metastasis,

3:47

but also apparently some nodes, um, as well.

3:49

And so we do the gallium 68 PSMA to determine

3:52

that there is a target for the ligand.

3:54

We need to make sure that the disease is PSMA expressing,

3:57

um, and then they are given lutetium 1 77 treatment, um,

4:00

and then imaged on a gamma camera

4:03

or a single photon emission tomography camera

4:05

one day post therapy.

4:07

And we wanna see that these match and they do.

4:09

So this is the posterior image, we can see all the uptake

4:11

through the spine, um,

4:12

in the proximal humerus lesions as well.

4:15

So that's very concordant, which is great.

4:18

So taking a case from my institution, here's the PSMA pet,

4:21

and again, you know, really widespread disease for the axial

4:24

and proximal appendicular skeleton.

4:26

Um, that bone marrow is quite, um, severely affected

4:29

and our patients will undergo a paired FDG PET as well

4:33

to ensure that the disease is PSMA expressing

4:36

and there are no lesions which are

4:37

what we call discordant disease.

4:39

So P smma negative and FDG positive

4:42

or where the FDG is so much more, um,

4:44

intense than the PSMA expression.

4:47

Um, and that's similar to what we saw in the prior module

4:49

with that liver case

4:51

where the liver lesion was intensely FDG AVID

4:54

but had no PSMA expression, we would call

4:56

that discordant disease.

4:58

Um, so in here, not too bad, even those small bone lesions

5:01

that, those bone lesions which have FTG uptake,

5:03

there's more PSMA expression.

5:05

So they would be well targeted by the therapy.

5:08

And so this is just the cross-sectional imaging

5:10

demonstrating that we've got diffuse bone disease,

5:12

multiple sclerotic lesions

5:14

through the skeleton corresponding to the PSMA uptake.

5:17

And this patient went on to have PSMA therapy.

5:20

This was post, um, approximately eight gigabit or dose.

5:22

And if we pop them side by side with the Gallium 68 pet, um,

5:26

you can see that the uptake in the skeleton is concordant

5:30

with the science of disease on the PET ct,

5:32

which is what we like to see.

5:34

So here just to conclude, is a bit of the evidence

5:37

for the efficacy of this therapy.

5:40

Um, so here's a couple of papers

5:42

that have actually come out of Australia.

5:43

Michael Hoffman and his group from um,

5:46

Peter McCallum in Melbourne

5:47

have been doing a lot of great work.

5:48

And so we're very proud to be Australian and,

5:50

and, um, being part of the world leading in this therapy.

5:54

So it's, you know, really been showing to

5:56

Have, have good results in patients

5:57

with metastatic castrate resistant prostate cancer.

6:00

So with high response rate, low toxicity, reduction in pain,

6:03

which is really important for patients

6:05

on palliative management.

6:07

And then also comparison with carbotaxel,

6:09

the PSMA has been leading to a higher response

6:12

and fewer grade three or grade four adverse events.

6:14

So, you know, significant adverse events

6:16

to the therapy as well.

6:18

So I watched this space, but it is becoming more

6:21

and more commonplace in the management of prostate cancer.