Radioisotopes for staging and follow-up of prostate cancer F. Scopinaro
Specific Radiotracers Gamma ray emitters Positron emitters 111 In capromab 111 In octreotide 99m Tc Tyr-octr. (more than one tracer) 99m Tc Bombesin 11 C Choline 68 Ga Bombesin
111 In Capromab Rationale: 111 In labelled anti MPSA Monoclonal antibody Use: Staging and to lesser extent radioguided surgery Results ( mainly american): 60 to 80% sensitivity,incomplete specificity
111 In/ 99m Tc and 123 I peptide agonists
Peptides directed towards G- protein coupled receptors Octreotide octreotate Tyr-octreotide Bombesin
G-PROTEIN COUPLED RECEPTORS
Choline IGF-I - 1. Somatostatine Plasma membrane choline Ε2 αer Ε2 αer Y-P P-Y IGF-IR Gene transcription + 2. - Phosphorylation site SSR 1,2,5 BNS 1,2,3 + + 2. Bombesin Cell nucleus Cell division B.
Endocytosis and recycling of cell surface receptors Cell surface receptor GRP-R recycling endocytosis New Synthesis Golgi Coated vesicle endosomes lysosomes degradation nucleus Cell membrane Figure 2.
Labelled Amphibian BN: peptide structure ( Demokritos Natl.center) 99m Tc[Leu 13 ] Bombesin ( 99m Tc BN) Cys-Aca-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His- Leu-Met-NH 2 N terminal changed in: Cys labelling Spacer arm; Aca:Amino esanoic acid Tc Binding-to-receptor site m Tc BN is a labelled amphibian bombesin; it shows actions of: eurotrasmitter, releasing factor, morphogen, tum. growth factor
Bombesin (BN) receptors Brain Thalamus Amigdala Hippocampus Olphactory areas Brain stems Outside Brain Smooth muscle of colon Gastrin secr. Cells Epithelial cancers (breast, prostate, colon) Stem cells (unpublished data)
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 B P 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
111 In Octreotide SPECT: prostate carcinoma Bladder Prostate Bladder Prostate
TRANSAXIAL SLIDES MRI + 99m Tc BN 99m Tc BN R 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 111 In 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 11 C 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 Linfonodo Ca Prostata, 1 linfonodo Otturatorio invaso Ca Prost. Prostate Ca, 2 invaded nodes (withdrawn with radio guided surgery ) Ca Linfonodi
DFG PET 99m Tc BN, planar reference for SPECT
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 99m Tc MDP bone scan: Diffuse metastatic bone uptake
CHEST, PLANAR SCAN 99m Tc BN 111 In Octreotide
Ant. Post met 99mTcBN, whole body scan, Patient with metastases on bone and soft tissue met
99m Tc EDDA-HYNIC Tyr-OCTEOTIDE distant soft tissue metastases with neuroendocrine shift # # # # # # # # # # # # # # # #
EDDA-HYNIC Tyr Octreotide, 40 min after I.V. administration ####### ####### MET Kidney
Results (very Preliminar, only 5 patients with both tracers) 99m Tc BN and 111 In octreotide, as well as 99m Tc 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.
Conclusions The use of 99m Tc 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 99m Tc BN is very promising for radioguided surgery The uptake of 99m Tc BN and 111 In octreotide is probably a method for addressing therapy
adiofarmaci con informazione complessa: bombesina/ adenoma rost. Scintigrafia negativa
Radiofarmaci a informazione biologica complessa: Bombesina/Ca prostata
Gastrinoma in a patient with atrophic gastritis and high basal secretin