 Thank you very much, Mithusha. It's both a pleasure and honor for me and today I'll be talking something different. I've had over the years occasion to talk on prostate cancer, but it's mostly been to do with multi parametric MR imaging and how things have changed over the years. I remember from endorectal MR that we used to do with the endorectal coil beginning in the year 2004 to today when multi parametric MR has become actually the modality of choice for prostate cancer diagnosis as well as for local regional staging. Today I've been asked by Dr. Sikandar to speak on the nuclear medicine aspects of prostate cancer and how that actually is where it falls in the entire armamentarium of imaging of prostate cancer. So, I hope you can see my slide. Yes, sir. Just trying to get it into, yes. So we'll talk today about imaging with nuclear medicine and theranostics. Now, one may wonder why is a radiologist talking about this. Actually, in the year 2000, 1999, actually Gangaram Hospital had approached me that they want to start an apartment of nuclear medicine and I had worked before that 1990 to 92 as a radiologist at INMAS, which is the preeminent institution at least was at that time for nuclear medicine in the country. Also got the country's first MRI in 1988 and that's how I actually got interested in nuclear medicine and started the center in the year 2000 in Gangaram Hospital and in 2006 we got the PET CT and I'll share with you and we've been since 2003 having DNB candidates in nuclear medicine and I'll share with you some of what we've done in the field of prostate cancer. Now, as you know, prostate cancer is the second most common cancer and the sixth most common cause of cancer death in men. When detected early, prostate cancer has more than a 90% cure rate. It's really looked upon today as a chronic disease rather than as cancer in the term that we tend to understand it. The treatment is highly individualized and molecular imaging technologies are dramatically improving the ways in which prostate cancer is diagnosed and treated. We know there's a variety of modalities available. We have the PET scan for a long time to look at bones. We had the technician bone scan over the last 15 years. There's also been waxing and waning interest in whole body diffusion weighted MR to look at the spread of prostate cancer. Of course, CT has its own role for spread, which now with PET CT being there, CT forms an important component from structural imaging standpoint. Of course, ultrasound, when you suspect a prostate problem, ultrasound is the first modality that is used and based on the suspicion that one may have or what one may find on ultrasound and Doppler, then really now it's established that one would go on and get a multi-parametric prostate MRI done and there also we have the multi-parametric and also the faster bi-parametric where you do a T2 weighted axial and diffusion and that also is showing a lot of promise but that's not the focus of my talk today. We will be focusing instead on where nuclear medicine modalities are playing an important role in this. Now, most of prostate cancer, most of cancer imaging on PET scan uses FDG which is fluorodeoxyglucose F18 and unfortunately in prostate cancer this had a very, very limited role. Both in primary diagnosis, staging and restaging of prostate cancer because prostate malignancies by and large are not FDG avid. They do not concentrate FDG within them but yet in certain limited instances, especially when it's poorly differentiated prostate malignancy, there may be FDG uptake and that really points to a poor prognosis. So, till PSMA which we will talk about in detail, prostate specific membrane antigen PET CT came in, FDG PET had hardly any role in imaging and that's the time also when whole body diffusion weighted imaging actually in the year 2009-10 when it became available it was showing promise till the time the PSMA PET came in. The limitations also of FDG PET are renal excretion of tracer in the urinary brada can hinder visualization of primary tumor and pelvic lymph nodes and that's why as in most cases when we are looking at the pelvis in any malignancy, we make the patient void, we even take delayed images so that we are able to overcome this limitation. FDG PET even has a very limited role in detecting osseous metastasis. Now gallium 68 PSMA PET CT and this we started, we were amongst the first few private institutions in the country which started doing PSMA PET CT in the year 2014 that's nine years ago and this uses a gallium generator. Now for those, I'm sure everyone knows but for the BGs who may have joined here, the FDG which is the preeminently used isotope is produced by a cyclotron. So FDG cyclotron produces it, it has a half-life of 1 hour 15 minutes and quickly from the cyclotron these companies rush the isotope to us and we use it for scanning. On the other hand, gallium 68 PSMA is a generator. It is a generator which is lying in our radiology, in our nuclear medicine departments and from this we elude the substance and then actually in a way marry it with PSMA so that we are able to do PSMA PET. So this is something which is available in-house of course the generator is very expensive costs nearly about 20 lakhs and it lasts really for about 8 to 9 months. So it's an expensive proposition but yet if we look at the cost versus benefit ratio of a PET CT it I think is weighed very very heavily towards benefit. Now prostate specific membrane antigens is expressed on the cell surface and is an integral membrane protein which is over expressed manifold in prostate cancer cells. It is not released into circulation and internalized after antibody binding to this called receptor mediated endocytosis and this PSMA is an excellent target for radionuclide imaging and also as we'll see later for therapy in prostate cancer. Now this is just an example to show you what is the difference in the same patient between a FDG PET CT and a PSMA PET. So this first image on the left is a FDG PET CT where you do see some uptake in these vertebral bodies and in the pelvic bones but just look at this. This is PSMA PET CT. It is so very avid you're able to pick up many more lesions which were not seen and this actually look at all the osseous lesions that are picked up. So this is the power of PSMA PET that even small lesions, tiny lesions, early lesions can be picked up be they osseous or in the lymph nodes or within the prosthetic bed itself. Again the same look at this FDG PET CT and look at that uptake on a PSMA PET CT. So one thing to clarify is that in case you want to do a PET CT in prostate cancer you have to specifically ask for a PSMA PET CT and not just write PET CT. Now what are the indications for gallium PSMA PET CT? It can differentiate BHV from carcinoma prostate. This is an indication which is rarely used. Targeted biopsy can be done after a previous negative biopsy in patients with high suspicion of prostate cancer. We do know that fusion biopsy is the preferred mode for prostate cancer where fusion is done of the multi-parametric MRI with the ultrasound and it's on that ultrasound guidance using this fusion which is how biopsy is done. But even there sometimes biopsy may fail because the lesion may not be as clearly depicted on the MRI and this is where in a failed biopsy PSMA PET CT can show exactly the location of the lesion and targeting can be done. Then it's useful of course in primary staging in high risk disease before surgical procedures or planning external beam radiation. It's important and useful in localization of tumor tissue in recurring prostate cancer. Now this is one area where we've done quite a bit of work and until now in these last nine years we've done about 5500 PSMA PET CTs. One of the major indications is when there is recurrence suspected because of rising PSMA after radical prostatectomy or after radiotherapy. The PSMA levels keep rising and that's when we know as radiologists that ultrasound and MRI haven't really been very useful. Unless it's a very prominent recurrence. This is one area where it's very, very useful apart from looking at primary disease staging. Then it's useful in monitoring treatment response to know whether your treatment is working or not. And in staging before and during PSMA directed radiolabeled therapy which is mainly in metastatic castration resistant prostate cancer. And we will talk about this Theranostics using Lutetium therapy which is again something which is PSMA mediated. Now in diagnosis this is a 63 year old male suspected carcinoma prostate with raised serum PSA levels. And this is as you can see here grossly enlarged prostate gland but you don't see any focal uptake of PSMA in any in the prostate. So here you can see that there's no abnormal uptake and so we are dealing with most likely a benign prostatic enlargement. This is another 64 year old male suspected CA prostate and most of these patients have had their multi parametric MRI done before. In most of them a lesion is suspected, it is found and then PSMA PET CT is done for further staging. So let me point out that for primary diagnosis of prostate cancer I would still rely more on multi parametric MRI and the PSMA PET CT is supplemental as regards the primary prostate cancer but is more useful for looking at lymph node metastases and of course for distant metastases because this is where the spread can be found out. So whole body PET CT and you are able to see spread and here this is the CT and then suddenly you start seeing these brights uptake within the prostate gland and so this was a patient with a PSA of 44, biopsy done four times always picked up benign tissue and so with this we are absolutely certain that we are dealing with prostatic malignancy and based on this the biopsy was directed and this did turn out to be Gleason's 3 plus 4 lesion. This is a 65 year old suspected CA prostate, race serum PSA and here what you can see is this small area of uptake and this turned out to be Adenocarceroma. So for me as a radiologist actually this helps me because apart from looking at the CT images it tells me exactly where to look based on the uptake. So many times usually in most of other cancers we do a CCT with PET in prostate cancer we do it as and when necessary and so apart from the intravenous contrast this is another contrast where things actually light up like a light bulb that is how explicitly sensitive this PSMA PET is for cancer of the prostate. For staging again like I said this is a 62 year old recently diagnosed CA prostate serum PSA 33 and with that we know that this is not just going to be confined to the prostate so after the MRI has been done here you see this lesion which is shown showing uptake and what you can see is that there are no distant metastases again this turned out to be a 4 plus 4 lesion Gleason's 8. 68 year old recently diagnosed PSA 80 and here what you can see you can see of course the primary lesion this is the urinary bladder which also shows concentration of the isotope as you can see here as well but here you see the lesion in the prostate and you can see the iliac bone metastases fairly large with the soft tissue component and also metastatic deposits seen within the vertebral bodies along with nodal meds which you are able to see so what PSMA PET CT does better than MRI better than even diffusion weighted MRI where we generally use a B value of 1500 to 2000 is that lesions within distant lesions as well as lymph node lesions are picked up much more sensitively than what MR can and of course you can do multi modality fusion gallium PSMA PET CT can be fused offline with all these software exists with most of the new MR's and PET CT's and so once you've done MR we just heard a talk on the PET MR and here again we are using the power of MR along with the power of PET and these can be fused the MR of course has limitations in the chest in the lungs but since most of these patients already have had this done we can always use the previous MRI and fuse the two of them together to show the PET MR kind of lesion for treatment response evaluation it's again useful of course PSA levels themselves are also very useful but to see spread or to see the patient who had baseline had this liver met and you can see on follow up after treatment the lesion has become larger and also there's another lesion that we are seeing and so this is again baseline there was no uptake within the spine whereas here you're able to see uptake within the vertebral bodies so this definitely is a treatment that is not working now for recurrence and this is where this modality holds its own this is a post radiotherapy CA prostate rising PSA levels which rose from 0.05 to 0.6 nanograms per ml and here what you see is local recurrence here the small little lesion which you're able to see on the left side within the prosthetic you know the residual prostate remember this was post radiotherapy so the prostate though shrunken is still there and here you're able to pick up this would have been in fact an MR had been done and it wasn't able to pick up and I know as someone who's really more into MR than into PET CT that these are difficult even in post radiotherapy scenario they are difficult to pick up on MR and are very very tough in post radical prostatectomy now I'll share with you our experience which started like I said in 2014 and in the first five years we had done more than 4,000 PSMA PET CT scans so probably we've done more than 5,500 that I mentioned and we've done three thesis topics on this and in RSNA 2018 I had actually presented you know our data at that time it was I think 3,500 cases that we had presented in 2018 now in the first one we looked at the role of PSMA PET CT in patients with recently diagnosed oblique suspected carcinoma prostate there were 150 patients and our results were that we found a sensitivity of 90% a specificity of 80% a positive predictive value of 95% so when you found it you know it was very likely to be prostatic malignancy however the negative predictive value is low significant but still low which means that if you get a negative PSMA PET CT that doesn't still you know conclusively rule out the presence of a lower grade of prostate cancer 3 plus 3 even 3 plus 4 at times so most of them tend to be avid the overall accuracy was 88% which is very very high in the second you know research thesis we evaluated the role of PSMA PET CT in patients with biochemical recurrence of prostate cancer after definitive treatment 170 patients analyzed and correlated the findings with pro-streatment serum PSA levels and here determining whether recurrence is local within the prostate or at the urethral bladder anastomosis regional that is pelvic or distant disease is critical when considering appropriate further treatment options and early localization of disease recurrence after definitive treatment of prostate cancer is vital to determine suitability for salvage treatment now morphological imaging methods are fairly poor in picking up biochemical recurrence as are 18 FFTG or even 18 11 Carbon Choline and these were all you know work which was done before 2013 2014 when PSMA actually became available commercially in Europe and we were able to bring it from there and so this was our aim to localize and restage carcinoma prostate using this modality in patients with biochemical recurrence and to determine the relationship between detection rate of PSMA PET CT and serum PSA level along with the Gleason score and like I said you know we analyze these patients we included men with suspected recurrent prostate cancer based on an elevated post treatment level of more than 0.2 nanograms per ml after radical prostatectomy and over a threshold of 2 nanograms 10 times above the nadir value post radiation therapy the data collected also analyzed the relationship of pre scan PSA level and prior Gleason score to the probability of a positive scan finding for recurrent prostate cancer in 170 patients 124 had previous radical prostatectomy and 46 had prior radiotherapy the median serum PSA in the radical prostatectomy group was 1.8 nanograms and 5.2 in the post radiotherapy group and what we found is that the detection rate of gallium was 39.3% for PSA which was between 0.2 to 0.5 nanograms so very low levels 0.2 to 0.5, 47% for PSA 0.5 to 1, 68% for PSA 1 to 2 and 93% so very high percentage for PSA more than equal to 2 now this finding was actually at variance with what had been reported at that time in literature and those numbers were very small this number of 124 was relatively nearly 6 or 8 times larger than that number I need to tell you that PSMA PET got FDA approval US FDA approval only in October of last year so in the US whatever PSMA PET was done was only done as a research tool for research and only after the US FDA has given approval have the numbers started coming up we were lucky that we were given the permission to use this much earlier in 2014 so in this group local recurrence was identified in 28% and lymph nodal metastasis in 65% so important to note that lymph nodal meds are also responsible for rising PSA levels and it's not necessary that you have to find local recurrence in the prostate bed itself and this is just showing that and this is to show that as the PSA level rose the detection rate also rose and these are actually the sites of recurrence in the post RP group now the detection rate in post radiotherapy group was 88.8% for PSA 2 to 4 remember we had taken patients who were more than 2 in the post radiotherapy group so the detection rate was very high nearly 90% and it was 100% for PSA level more than 4 and so this is something which is quite dramatic, quite dramatic local recurrence after the radiotherapy was present in 80% of this group and 63% so had lymph node metastasis so note that between those who had radical prostatectomy we said the number of local recurrence in the prosthetic bed was 28% whereas it is nearly 80% in post radiotherapy group the prostate hasn't been removed maybe there's a message in this and we need to work more on this aspect and the lymph nodal metastasis numbers were 63% there, 63% here and this is again to a graphic representation of the same now what was the relationship of Gleason score with detection efficacy now if you look at that increased detection rates with increasing Gleason scores were seen detection rate 63% for Gleason score less than equal to 7 which increased to 76% for Gleason score more than equal to 8 so as the Gleason score rose the detection rate increased now this is a 73 year old adeno CA post radical prostatectomy and here you can see a small recurrence in a lymph node here was it disease which was not identified at the time but this is what a small sub centimeter lymph node showing FDG uptake this is a 61 year old radical prostatectomy pelvic lymphedinectomy raised PSA 3.8 and here you see PSMA avid Gleason in the prosthetic bed you see it here and of course domino pelvic lymphenopathy you see this in the lymphatic bed here 61 year old post radiotherapy his PSA rose from 0.72 at the baseline to 9.5 and here you see you know PSMA avid Gleason in the prosthetic bed as well as lymph nodal metastasis that you can see very well and this is another one Gleason score 8 post prostatectomy post adjuvant RT on hormonal therapy and with race serum PSA 3.5 and here again you can see the lesion in the bone you can see lesion within the prostate gland itself and lymph nodal metastasis all can be seen in recurrence there is of course the patient who had everything post radical prostatectomy PSA 29.5 and here you can see he has so many bony lesions which are detected very very easily there is also a left supraclab lymph node which is seen and surprisingly no lymph nodes seen in between now this is a paper we published in 2020 in the Indian Journal of Urology which was for localizing and restaging of carcinoma prostate and histopathology done and here what we found that out of 30 patients 16 had PSMA avid left pelvic lymph nodes and 18 had right pelvic lymph nodes on histopathology 19 patients were positive for left pelvic lymph node metastasis and 14 for positive were positive for right pelvic metastasis in the lymph nodes and on correlating both the results of gallium PSMA and histopathology the cones kappa value came to 0.68 for left side lymph node and 0.64 for right side and anything between 0.6 and 0.8 signifies substantial agreement or concordance and so this is useful so you know this is this is a case again ill-defined lesion you see in the prostate and there is this lesion here within the lymph node you can see a lesion here as well depicted now in conclusion theranostics and this is something again that we've started about six months ago in one of our centers for theranostics for treatment for those calculation we also need a gamma camera so you need a gamma camera along with a PET CT if you have only a PET CT alone you will not be able to do therapy now theranostics is the combination of a diagnostic tool that helps to define the right therapeutic tool for a specific disease and in nuclear medicine theranostics is easy to apply and understand because of an easy switch of the radionuclide from diagnosis to treatment on the same vector and we all know radio iodine therapy which has been around for a long long time so here what is done is that the same PSMA is actually used and here instead of giving a diagnostic dose we give a much higher dose and we know that this PSMA is going to go and concentrate in the cancer cells they may be located anywhere in the body and so this is what is being used to actually treat and these are all patients now the inclusion criteria are multiple these are patients who failed everything you know and they are resistant to hormonal therapy they have extensive disease and so this is something which is helping this has been around now since some time and more and more patients are coming in for lutetium therapy with PSMA so there are some inclusion criteria of course the WBC levels have to be and remember these are all patients who are quite sick since it's extensive disease 2000 hemoglobin more than 8, platelets more than 75,000 creatinine should be less than 2 we rule out obstructive renal disease and the ECOG should be less than equal to 2 and what is ECOG? There is a ECOG performance scale and this actually is showing us the physical and capability of a patient ECOG score of 0 is when someone is fully active I'm going into this because this is something which we as radiologists actually don't really know about at least I didn't know about it 0 is fully active able to perform all pre illness activities without restrictions 1 is there is limitation in vigorous physical activity but he can stand and do soft work for example mild home and office work 2 is standing and doing his own work but unable to work and able to spend more than half of the daylight hours on his feet these are the people who will fall in the criteria to undergo lutetium therapy in their given clinical setting those who are in 3 and 4 where they have difficulty in self-care sleeping for more than half of the daylight hours or sitting in a chair or cannot self-care fully dependent on chair or bed these are patients who are as yet not to be included for lutetium therapy before treatment of course we need to get a good history from the patient collect information about pre-treatment stage of the disease the treatments that have been applied previous procedures pathology results everything so you know we as radiologists or nuclear medicine specialists need to do this very very thoroughly then we gallium 6 PSMA scan should have been done at least within 2 weeks before the treatment within that 2 week period if it has been done earlier then we need to repeat it of course complete blood count biochemistry and of course other biochemical parameters it's given intravenously takes about 30 minutes for the drug to infuse into the bloodstream of course we need to give anti nausea medicines and diuretics diuretics help to flush the lutetium from the system as quickly as possible and this is a outpatient treatment after you've given it patient has to wait in the department for a few hours or longer of course it's a special room shielded room where the patient is injected and waits and once his radiation levels start coming down within about 4 hours you can send him back home a day after treatment he'll have an imaging test a spec scan this checks to make sure therapy hit the right targets and it's a dosimetry scan it shows you where all the lutetium concentrated there can be side effects dry mouth dry eyes nausea of vomiting fatigue most of these symptoms go away in a few days there's a small chance dry eyes and mouth can be permanent a few people have a dip in blood counts because lutetium can affect the bone marrow lutetium can also target healthy organs that have very small amounts of PSMA like the salivary glands and that's why you get a dry mouth small intestine and the kidneys the recommended dose of course is about 200 micro curies and you know you inject this in 2 to 3 minutes and follow it with 500 ml of normal saline infusion over the next 30 to 40 minutes now how often can we give this depending on the response lutetium 177 can be administered every 4 to 6 weeks and till a maximum as yet of 6 doses of course depending absolutely on how the treatment affected and the side effects that a patient may encounter now this is one of our cases this is a initial free therapy image where you can see extensive metastatic disease and remember these are patients where everything has been tried surgery, radiotherapy, hormonal therapy, castration whatever everything has been tried and this is the final final treatment this is the change you see after the first cycle there is reduction in both the number as well as the size of the lesions further reduction after the second cycle and this nearly complete clearance after the third cycle and actually if necessary one today has the approval to go up to six cycles so like I said FDA, US FDA gave its approval on March 23, 2022 and like I said these are you know PSMA positive metastatic castration resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxin based chemotherapy still there is no response and of course it can be given every 6 weeks for up to 6 doses or until the disease progression or unacceptable toxicity so in conclusion let me say that prostate cancer which is a very very common cancer most of us would know some patient amongst our friend circle or amongst our relatives the PSA levels and it has been controversial whether PSA should be routinely done as a part of a health check or not I for one would say that I err on the side of doing it at least once a year and if there is suspicion of prostate abnormality then the first test to be done is an ultrasound if the PSA level is such and clinically you suspect remember the prostate cancer also has genetic undertones so then after that you do a multi parametric prostate MRI try to localize the lesion then a fusion biopsy if you have the fusion system or biopsy by whatever means that a radiologist or a urologist is familiar with and following that what I've talked about the PSMA PET CT and where necessary as a life-saving procedure the lutetium therapy. Theranostics I would say is not the future it is the present it is about personalized and precision molecular radiation therapy thank you so very much for a patient hearing and for giving me this opportunity to share some of our work with you thank you