Background. Choline presents a high affinity for maligna nt prostate tissue. It can be labelled with positron emitting 18f,and used for the evaluation of patients with prostate carcinoma by PET/CTimaging. The aim of this paper is tosummarise our experience with fluoromethylcholine ('8f-choline) PET/CTin patients with prosta te cancer. Methods. In 4 months we investigated the patients with histopathological (or cytological) confirmed prosta te cancer. Two observers evaluated the early and late 18f-choline PETimages in correlation with corresponding localising CT images and using the semiquantitative standard uptake value (SUV)calculation. Results. The 18f-choline PET/CT was made in 50 patients with prosta te cancer. There were 18 patients after radical prostatectomy and 32 without surgery.ln allpatients wiff1but surgery the pathological uptake was seen in the prostate. ln 14 (44 %) patients of this group there was evidence of metastatic spread in local or distant Iymph nodes and/or bones. In out of 18 patients after radical prostatectomy the local recurrence was detected in 6 patients (33%) and distant metastases were present in 2 patients (10%). Conclusions. 18f-choline PET/CTseems to be useful imaging modality in patients with prosta te carcinoma; it can demonstrate spread of the disease preoperatively and detect the local recurrence after radical prostatectomy.
COBISS.SI-ID: 28076505
PURPOSE: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 (111)In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. METHODS: Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with (111)In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. RESULTS: Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrinanalogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides,a cyclized peptide and a divalent peptide were tested. CONCLUSION: Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may therefore be good candidates for future clinical studies.
COBISS.SI-ID: 3067505
The development of metabolically stable radiolabeled gastrin analogues with suitable pharmacokinetics is a topic of recent research activity. These imaging vectors are of interest because the gastrin/CCK2 receptor is highly overexpressed in different tumors such as medullary thyroid cancer, neuroendocrine tumors, and SCLC. The drawback of current targeting agents is either their metabolic instability or their high kidney uptake. We present the synthesis and in vitro and in vivo evaluation of 11 111In-labeled DOTA-conjugated peptides that differ by their spacer between the peptide and the chelate. We introduced uncharged but hydrophilic spacers such as oligoethyleneglycol, serine, and glutamine. The affinity of all radiopeptides was high with IC50 values between 0.5 and 4.8 nM. The improvement of human serum stability is 500-fold within this series of compounds. In addition the kidney uptake could be lowered distinctly and the tumor-to-kidney ratio improved almost 60-fold if compared with radiotracers having charged spacers such as glutamic acid.
COBISS.SI-ID: 2988401