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Radioisotopes for staging and follow-up of prostate cancer F. Scopinaro Specific Radiotracers Gamma ray emitters • • • 111In capromab 111In octreotide 99mTc Tyr-octr. (more than one tracer) • 99mTc Bombesin Positron emitters • • 11C Choline 68 Ga Bombesin 111In Capromab • Rationale: 111In labelled anti MPSA Monoclonal antibody • Use: Staging and to lesser extent radioguided surgery • Results ( mainly american): 60 to 80% sensitivity,incomplete specificity 111In/99mTc and 123I peptide agonists Peptides directed towards Gprotein coupled receptors • • • • Octreotide octreotate Tyr-octreotide Bombesin G-PROTEIN COUPLED RECEPTORS Choline - IGF-I 1. Somatostatine Phosphorylation site IGF-IR Plasma membrane choline Y-P P-Y + Ε2 αER Ε2 αER Gene transcription Cell division 2. Bombesin SSR 1,2,5 BNS 1,2,3 Cell nucleus B. 2. - + + Endocytosis and recycling of cell surface receptors Cell surface receptor GRP-R recycling endocytosis New Synthesis Coated vesicle endosomes degradation Golgi Cell membrane Figure 2. lysosomes nucleus Labelled Amphibian BN: peptide structure ( Demokritos Natl.center) 99mTc[Leu13] Bombesin (99mTc BN) Cys-Aca-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-HisLeu-Met-NH2 Spacer arm; Aca:Amino esanoic acid N terminal changed in: Cys labelling Tc Binding-to-receptor site 99mTc BN is a labelled amphibian bombesin; it shows actions of: neurotrasmitter, releasing factor, morphogen, tum. growth factor Bombesin (BN) receptors Brain Outside Brain • • • • • • Smooth muscle of colon • Gastrin secr. Cells • Epithelial cancers (breast, prostate, colon) • Stem cells (unpublished data) Thalamus Amigdala Hippocampus Olphactory areas Brain stems Glandular and neuroendocrine Prostate cancer • Gland. Prostate cancer: Overexpression of Bombesin receptors: NMB preferring or BNS 1( 5 to 10 %), GRP preferring or BNS 2 ( 80 to 90%), orphan BNS 3 (3 to 10), SSR1 and SSR5 • Neuroendocrine prostate cancer: SSR subtype 2. • others? Prostate cancer with inconclusive Phase-Array NMR study: diagnosis with 99mTc Bombesin SPECT. B P B U U MRI BN SPECT FUSION IMAGE P: Prostate; B: Bladder; U: Urethra Prostate cancer Accepted for publlication, Eur.J. Nucl. Med mol Im, 18 june 2003 111In Bladder Prostate Bladder Prostate Octreotide SPECT: prostate carcinoma TRANSAXIAL SLIDES MRI + 99mTc BN R 99mTc BN L Prostate cancer 111 In octreotide SPECT: negative findings Results ( at the moment) • 22 patients with PSA 4,1 to 10 ng/ml, 14 cancers • 99mTc BN: Se= 100%; Sp= 100% ( 22 patients, 14 with final diagnosis of cancer ) • Uptake of 111In octreotide: 2 patiens out of 8 (10 out of the 14 patients with positive BN SPECT) Staging (lymph nodes) • N staging in prostate cancer is difficult with current imaging methods, including 18F DFG PET • 11C Choline PET and Choline/acetate NMR spectroscopy are effective though not easily available • Detection of invaded lymph nodes can open a new field in radioisotope guided surgery 99mTc BN SPECT Ca Prostata, 1 linfonodo Otturatorio invaso Linfonodo Ca Prost. Ca Prostate Ca, 2 invaded nodes (withdrawn with radio guided surgery ) Linfonodi 99mTc BN, planar reference for SPECT DFG PET Radioguided surgery with portable high resolution imaging device Radio guided surgery: Lymph node image during operation Results ( at the moment) • Nine patients with inconclusive findings at CT and NMRI before operation: detection of invasion, 100% Sp (surgical and pathological validation) • two patients successfully operated with radioguided surgery Distant metastases • Bone scan easily detects bone metastases metastases: it is cheap and everywere available • Neuroendocrine shift can be detected on blood with RIA chromogranine assay. This method does not localise shifts • BN and SS detect and localise the shift Prostate cancer patient 99mTc MDP bone scan: Diffuse metastatic bone uptake CHEST, PLANAR SCAN 99mTc BN 111In Octreotide Ant. Post met 99mTcBN, whole body scan, Patient with metastases on bone and soft tissue met 99mTc EDDA-HYNIC Tyr-OCTEOTIDE distant soft tissue metastases with neuroendocrine shift # # # # # # # # # # # # # # # # EDDA-HYNIC Tyr Octreotide, 40 min after I.V. administration ####### ####### Kidney MET Results (very Preliminar, only 5 patients with both tracers) BN and 111In octreotide, as well as 99mTc Tyr-Octreotide are able to detect the neuroendocrine shift of metastases. These tracers are also able to detect soft tissue metastases • When neuroendocrine shift occurs it does not affect all the metastases. • 99mTc Conclusions • The use of 99mTc BN for diagnosis, staging and follow-up of prostate cancer is still a matter of research. Results are very promising but have to be confirmed • 99mTc BN is very promising for radioguided surgery • The uptake of 99mTc BN and 111In octreotide is probably a method for addressing therapy Radiofarmaci con informazione complessa: bombesina/ adenoma prost. Scintigrafia negativa Radiofarmaci a informazione biologica complessa: Bombesina/Ca prostata Gastrinoma in a patient with atrophic gastritis and high basal secretin