Molecular Imaging and Therapy in

Prostate Cancer

Dr Ameya Puranik DNB Consultant, Nuclear Medicine and PET/CT, Bombay Hospital, Mumbai

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.???

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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

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

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

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

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

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

TcTX-P104-01-02

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SPECT-CT

CT

January 2011 June 2011 99mTc-MDP 99mTc-MDP 99mTc-MIP-1404

March 2011

Disease progression iden7fied by PSMA imaging poten7ally earlier than bone scan

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

Lets decipher it. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC 68Ga Radionuclide Glu-urea-Lys(Ahx) PSMA inhibitor HBED-CC - Chelator

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) 41:1120

68Ga-PSMA

18F-fluoromethylcholine

Afshar-Oromieh, Haberkorn, et al Eur J Nucl Med Mol Imaging (2014) 41:1120

68Ga-PSMA Outperforms 18F-Choline in DetecRng PCa

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

Ga 68 PSMA scan done.

LeT Common iliac node Concordant on PET and CT

CT normal.but Ga PSMA detected these nodes

AlsoaddiHonal findings.. NOT PICKED UP ON CT

Presacral nodule Skeletal metastases

Sternum Vertebral

Literature.

Krause BJ et al . EJNMMI 2008; 35: 1823.

PSMA PET/CT vs CI

Literature.

So.do we use it ATB in PC

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 90s 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.

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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

Anterior and posterior whole body scinRgrams of 131I-MIP-1095 in paRent 01 at 7(a), 10(b) and 17(c) days post injecRon

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

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

So.why are targeted radionuclide therapies not popular..?? - Absence of RCTs - DefiniHon of end point

Take Home Message Ga-68 PSMA PET/CT has definite indicaHon in recurrence sekngeven 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

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

THANK YOU. FOR YOUR ATTENTION..!!!!