Prostate Cancer and PSMA:

Transcription

1 Prostate Cancer and PSMA: The Clinical Perspective from Liverpool. Dr. Christopher Mayes. Professor Sobhan Vinjamuri. Department of Nuclear Medicine Royal Liverpool University Hospital (BSUR 2016 Plymouth)

2 PSMA : Clinical Perspective from Liverpool. Prostate Cancer and NM PSMA Diagnosis Setting up a 68 Ga PSMA Service PSMA as Therapy

3 PSMA : Clinical Perspective from Liverpool. Nuclear Medicine = Molecular Medicine. Medicine = Diagnosis + Therapy PET-CT F18 FDG

4 NM and Prostate Cancer Bone Scan for assessment of? Bone Mets. PET-CT Delineation of primary tumour for Dose escalated RT planning in Medium/High Risk patients. PET-CT Assessment of recurrence/metastatic disease. Radionuclide therapy of bone metastasis and bone pain palliation. Radionuclide therapy including soft tissue metastatic disease.

5 Prostate Cancer and PET-CT Prostate cancer well differentiated. PSA if less than 10 will usually mean no bone mets detected on conventional bone scan. Even with low PSA, short PSA doubling time suggest aggressive disease. Recurrence PSA following radical prostatectomy. 18 F Choline may detect distant mets. 68 Ga PSMA PET-CT can now help detect distant mets. very early. 60% mets detected PSA< % mets detected PSA>2.2 ng/ml The role of PSMA PET/CT imaging in restaging of prostate cancer patients with low prostate-specific antigen levels. Kabasakal, Levent; Demirci, Emre; Nematyazar, Jamal; Akyel, Resit; Razavi, Baresh; Ocak, Meltem; Aygun, Aslan; Obek, Can; Kural, Ali R. Less Nuclear Medicine Communications. 38(2): , February 2017 These may be soft tissue as well as bone mets!

6 The Bone Scan Imaging of Osteoblastic activity with 99m Tc MDP (methylene diphosphonate) incorporated into bone crystals. Osteoblastic repair of metastatic bone damage occurs long before anatomical changes apparent on X-Rays. Efficient Scanning of whole skeleton for mets. with small radiation dose. Routinely performed on Gamma Camera 3 hours post injection with 99m Tc MDP

7 99m Tc MDP Bone Scan

8 Prostate Cancer and PET-CT 200MBq 18 F Sodium Fluoride injected IV and scanned at 1 hour. Faster, more sensitive and better resolution than Gamma Camera imaging. Poor availability of PET-CT scanners in UK.

9 18 F PET-CT Bone 99m Tc MDP Gamma Camera Bone

10 Prostate Cancer and PET-CT Prostate Cancer usually well differentiated and slow growing. Low PSA and Gleason Score <7 Good prognosis. Bone pain investigated with NM Bone Scan alleviates worries of Bone Mets. Watch and wait or aggressive treatment of primary? Radiotherapy option-lesion usually defined by MRI/CT but PET-CT using 18 F Choline may also be useful for identification of Dominant Intraprostatic Lesion DiL for increased precision of escalated Radiotherapy Dose.

11 18 F Choline Identification of Dominant Prostate Lesions

12 Rapid Arc Radiotherapy Dose Painting

13 Prostate Cancer and PET-CT PSMA Prostate specific membrane antigen Restricted type II integral membrane cell surface glycoprotein. Unlike PSA it is not secreted but has increased expression in high grade cancers and metastatic disease and sits in cell membrane of CaP cells. Monoclonal antibody can target these proteins for imaging - 68 Ga PSMA PET-CT. Not quite as specific as name suggests.

14 68 Ga PSMA : Radiopharmacy Challenges. Short Half Life. Radiation Protection of Staff. Cost.

15 PSMA : Clinical Experience in Liverpool. 68 Ga available from generator acquired for neuro-endocrine scanning. 68 Ge half life = 271 days. 68 Ga half life = 68 mins. 68 Ga PSMA Scanning in Liverpool accepted with PSA>2. PSA<2 if agreed at MDT.

16 PSMA : Clinical Experience in UK. 3-4 Centres in UK scanning with 68 Ga PSMA. Royal Marsden available for self funding patients. Only UCL and Liverpool accepting NHS patients. PSMA not available on PET-CT national contract.

17 PSMA : Clinical Experience in Liverpool.

18 Pump for Hands Free Generator Elution.

19 PSMA :Radiopharmaceutical Synthesis Unit.

20 68 Ga PSMA : Radiopharmacy Synthesis Unit. What do you want to make? Do you want to do any R&D? What is your workload likely to be? What generator are you using? Do you want fully automated? Cost (not just module but consumables) Where are you going to put it? Hot cell/isolator/grade B clean room

21 PSMA : Clinical Experience in Liverpool. PSMA labelled with 68 Ga now 18 F PSMA under development Mol Imaging Biol (2015) 17:565Y574 DOI: /s * World Molecular Imaging Society, 2015 Published Online: 21 April 2015 Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer Zsolt Szabo, Esther Mena, Steven P. Rowe, Donika Plyku, Rosa Nidal,Mario A. Eisenberger, Emmanuel S. Antonarakis, Hong Fan, Robert F. Dannals, Ying Chen, Ronnie C. Mease, Melin Vranesic, Akrita Bhatnagar,George Sgouros, Steve Y. Cho, Martin G. Pomper.

22 PSMA : Clinical Experience in Liverpool. PSA 2 to 6 PSA 6 to 10 PSA > 10 PSA > Ga PSMA 18 F choline 18 F fluoride 99m Tc MDP

23 PSMA : Clinical Experience in Liverpool. No Preparation 68 Ga PSMA 150MBq(nominal). 500ml water. Scan 60mins post inj. Empty Bladder. PET Scan 5 mins. Pelvis, 3mins/field All other sections to vertex. Empty Bladder. 10 minute prostate bed view.

24 PSMA PET-CT scan demonstrating bone and soft tissue mets.

25 Prostate Cancer and PSMA PET-CT

26 Prostate Cancer and PET-CT PSMA Prostate specific membrane antigen. Clinical trials with PSMA with a Beta particle emitter for internal radiotherapy. Molecule latches onto CaP cells and treats bone and soft tissue mets with Beta Radiation. J Clinical Oncology. VOLUME 22 NUMBER 13 JULY Phase I Trial of Yttrium-90 Labeled Anti Prostate-Specific Membrane Antigen Monoclonal Antibody J591for Androgen-Independent Prostate Cancer Matthew I. Milowsky, David M. Nanus, Lale Kostakoglu, Shankar Vallabhajosula, Stanley J. Goldsmith, and Neil H. Bander

27 Prostate Cancer PSMA Therapy PSMA Therapy possible with 90 Y and 177 Lu. Clinical 177 Lu PSMA therapy in UK requires approval from ARSAC. Proximal tubule reabsorption and renal trapping seen on diagnostic scans. Kidneys require protection for therapeutic doses. Amino Acid inhibition of tubular resorption routinely used during Dotatate therapies for Carcinoids.

28 NM Therapy for Prostate Bone Mets with 223 Ra Dichloride (Xofigo) Clinically available now. Ra similar to Ca incorporated into bone crystals. 223 Ra Alpha particle emitter. Short range 100micron 2-10 cells means that bone marrow not significantly irradiated Low haematological toxicity. Clinically available now. Shown to control pain and increase survival. Unlike PSMA will not treat soft tissue lesions.

29 Acknowledgements Dr. Maggie Cooper RLUH Radiopharmacy. UCL cooperation and PSMA images.