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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.???
2
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
11
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.
27
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..!!!!
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