Molecular imaging and therapy in prostate cancer
•
6 gefällt mir•2,762 views
MISI lecture by Dr. Ameya Puranik (Consultant, Bombay Hospital), Piramal Tower, Mumbai 26-August-2015
Empfohlen
Weitere ähnliche Inhalte
Was ist angesagt?
Was ist angesagt? (20)
Andere mochten auch
Andere mochten auch (20)
Ähnlich wie Molecular imaging and therapy in prostate cancer
Ähnlich wie Molecular imaging and therapy in prostate cancer (20)
Kürzlich hochgeladen
Kürzlich hochgeladen (20)
Molecular imaging and therapy in prostate cancer
- 1. Molecular Imaging and Therapy in Prostate Cancer Dr Ameya Puranik DNB Consultant, Nuclear Medicine and PET/CT, Bombay Hospital, Mumbai
- 2. Prostate Cancer (PC) • PC is the second leading cause of Cancer among men lobally, more than 900,000 new cases of prostate cancer were diagnosed in 2010 … • Sixth leading cause of cancer deaths amongst men worldwide with more than 260,000 men died from the disease • According to the World Cancer Research Fund InternaHonal it is predicted the number of prostate cancer cases will almost double (1.7 million) by 2030 • Indian scenario….??? 2
- 3. 3 Prostate Cancer Imaging: 2.5m Annual Procedures Staging Response Relapse Detection • Newly Diagnosed 250,000 per year • 500,000 per year • Biopsy 1 M per year • 750,000 + per year Whole body imaging is needed to confirm and localize metastatic spread Standard of Care Imaging Falls short in all sectors: • CT scan • Bone scan • Endorectal MRI • PET-FDG scan • ProstaScint Intraprostatic imaging is needed to guide biopsy
- 4. PET tracers used in Prostate Cancer Cell Metabolism Glucose 18F-‐FDG Choline 11C-‐choline 18F-‐choline Acetate 11C-‐acetate 18F-‐acetate Amino Acids Leucine 18F-‐FACBC Methionine 11C-‐methionine Tryptophan 11C-‐5-‐hydroxy-‐ 18F-‐5-‐fluoro-‐ Nucleo-‐ sides 18F-‐FLT 18F-‐FMAU
- 6. “Big Bang” in Prostate Imaging • A disrupHve technological innovaHon that enters the market with a bang. • Big Bang DisrupHons… – experience dramaHc market adopHon right out of the gate, oQen causing unintended collateral damage to incumbent businesses. – consumers suddenly and enthusiasHcally abandon older and even defining invenHons for something new and oQen untested. Paul Nunes and Larry Downes @ forbes.com
- 7. PSMA: Structure and Func7on • 110 kDa, type II, highly glycosylated transmembrane protein • Member of a family of zinc-‐dependent exopepHdases with glutamate carboxypepHdase acHvity – NAALADase, FOLHI • Found in prostate, brain, kidney proximal tubules, intesHnal brush border membranes • Expression is increased in prostate cancer and tumor neovasculature Filamin A Binding CatalyHc DimerizaHon Glycine-‐rich Proline-‐rich Transmembrane N C Unknown FuncHon Extracellular Intracellular
- 8. • Trans-‐membrane receptor with a large extra-‐cellular domain • EnzymaHc acHvity allows for development of inhibitors and their internalisaHon aQer ligand binding. • Rapid internalisaHon leads to enhanced tracer uptake at opHmum doses and thereby good image quality • Moreover small molecules can easily be used allowing faster blood clearance and low back-‐ground acHvity.) • PSMA inhibitor pla^orm allows imaging and therapy by a_achment of different radionuclides to these small molecules
- 10. Whole body scan of biopsy posi7ve pa7ent with 99mTc-‐MIP-‐1404 prior to prostatectomy Anterior Posterior Abnormal findings in the gland at site of primary tumor
- 12. January 2011 June 2011 99mTc-‐MDP 99mTc-‐MDP 99mTc-‐MIP-‐1404 March 2011 Disease progression iden7fied by PSMA imaging poten7ally earlier than bone scan
- 13. High Affinity Leads Containing Gallium-68 for PET Ga-68: 68 min T1/2 M. Eder, M. Eisenhut, U. Haberkorn et al DKFZ [68Ga]-PSMA-HBED-CC
- 14. Lets decipher it…. 68Ga-‐labelled Glu-‐urea-‐Lys(Ahx)-‐HBED-‐CC 68Ga – Radionuclide Glu-‐urea-‐Lys(Ahx) – PSMA inhibitor HBED-‐CC -‐ Chelator
- 16. PaHent 12 (a, b) PaHent 18 (c, d) 18F-‐fluoromethylcholine 68Ga-‐PSMA 68Ga-‐PSMA Outperforms 18F-‐Choline in DetecHng PCa Afshar-‐Oromieh, Haberkorn, et al Eur J Nucl Med Mol Imaging (2014) 41:11–20
- 17. 68Ga-‐PSMA 18F-‐fluoromethylcholine Afshar-‐Oromieh, Haberkorn, et al Eur J Nucl Med Mol Imaging (2014) 41:11–20 68Ga-‐PSMA Outperforms 18F-‐Choline in DetecRng PCa
- 18. Case 1 – Clinical history • 82/M • K/c/o adenocarcinoma prostate • Radical prostatectomy with pelvic nodal dissecHon (Jan 1999) • RT to pelvis (March 1999) • Comes with suspicious recurrence • PSA 3.69
- 19. Ga 68 PSMA scan done…. LeT Common iliac node Concordant on PET and CT CT normal…….but Ga PSMA detected these nodes
- 20. Also…addiHonal findings….. NOT PICKED UP ON CT Presacral nodule Skeletal metastases Sternum Vertebral
- 21. Literature……. Krause BJ et al . EJNMMI 2008; 35: 18–23.
- 22. PSMA PET/CT vs CI
- 23. Literature…….
- 25. So….do we use it ATB in PC
- 26. THERANOSTICS - • Theranostics is the combination of a Diagnostic Tool that helps to define the right Therapeutic Tool for a specific disease – we see what we treat. • Used first by John Funkhouser/pharma industry at the beginning of the 90’s at the same time the concept of Personalized Medicine appeared. • In NM, THERANOSTICS is easy to apply and to understand, because of an easy switch of the radionuclide from Dx to Rx on the same vector. • The most prominent and oldest application is radioiodine. Molecular Nuclear Medicine and THERANOSTICS within MNM are definitely part of Personalized Health Care.
- 27. 27
- 28. 124I-‐MIP-‐1095 Pre-‐Treatment PET Scans: 124I-‐MIP-‐1095 PET images (maximal intensity projecRon) of paRent 01 as a funcRon of Rme Pt: WL 01
- 29. Anterior and posterior whole body scinRgrams of 131I-‐MIP-‐1095 in paRent 01 at 7(a), 10(b) and 17(c) days post injecRon
- 32. Pretherapy Ga-‐68 PSMA PET/CT Local prostate cancer involving the seminal vesicles with lymph node and extensive bone metastases. 3 months post Lu-‐177 PSMA Therapy Excellent response to radioligand therapy. Most of the intense PSMA posiHve metastases are not discernible anymore. THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka in collaboration with H.J. Wester, Chair Pharmaceutical Radiochemistry, TU Munich, Germany
- 33. Toxicity: Reduce the dose in low GFR or EC clearance Protect salivary glands with ice packs Early reports – Grade 1/2 hematotoxicity No reported nephrotoxicity
- 34. So….why are targeted radionuclide therapies not popular..?? -‐ Absence of RCTs -‐ DefiniHon of end point
- 35. Take Home Message • Ga-‐68 PSMA PET/CT has definite indicaHon in recurrence sekng…even with minimally detectable PSA levels • Not YET recommended for diagnosis and staging • Robust literature evidence is sHll awaited for establishing diagnosHc algorithms • Therapy using Lu-‐177 PSMA is a targeted therapeuHc opHon in treatment refractory cases and should be personalised
- 36. Acknowledgements PROF (DR) RICHARD P. BAUM DEPT OF MOLECULAR IMAGING & MOLECULAR RADIOTHERAPY, ZENTRALKLINIK, BAD BERKA, GERMANY PIRAMAL GROUP DEPT OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, TATA MEMORIAL HOSPITAL, MUMBAI
- 37. THANK YOU…. FOR YOUR ATTENTION……..!!!!