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Bombesin (BBN) is a peptide showing high affinity for the gastrin-releasing peptide receptor. Tumors such as prostate, small cell lung cancer, breast, gastric, and colon cancer are known to over express receptors to BBN and gastrin-releasing peptide (GRP). The goal of this study was to evaluate a new (67)Ga radiolabeled BBN analog based on the bifunctional chelating ligand DOTA (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid), which could be used as a tool for diagnosis of GRP receptor-positive tumors. DOTA-GABA-BBN (7-14) NH(2) was synthesized using a standard Fmoc strategy. Labeling with (67)Ga was performed at 95°C for 30 minutes in ammonium acetate buffer (pH = 4.8). Radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was examined in the presence of human serum at 37°C up to 24 hours. The receptor-bound internalization and externalization rates were studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in nude mice bearing PC-3 tumor. Labeling yield of >90% was obtained corresponding to a specific activity of approximatrly 2.6 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed a good and specific internalization into PC-3 cells (16.13% ± 0.71% at 4 hours). After 4 hours, a considerable amount of activity (52.42% ± 1.86%) was externalized. In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in GRP-receptor-positive organs. After 4 hours, the uptake in mouse tumor and pancreas was 1.30% ± 0.18% ID/g (percentage of injected dose per gram of tissue) and 1.21% ± 0.13% ID/g, respectively. These data show that [(67)Ga]-DOTA-GABA-BBN (7-14) NH₂ is a specific radioligand for GRP receptor positive tumors and is a suitable candidate for clinical studies.

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In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors.