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Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 , RM26) conjugated to 1,4,7-triazacyclononane- N , N ', N ''-triacetic acid (NOTA) via a diethylene glycol (PEG 2 ) spacer (NOTA-P2-RM26) labeled with  68 Ga and  111 In. We found that this conjugate has favorable properties for  in vivo  imaging of GRPR-expression. The focus of this study was to develop a  18 F-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with  18 F using aluminum-fluoride chelation. Stability,  in vitro  binding specificity and cellular processing tests were performed. The inhibition efficiency (IC 50 ) of the [ nat F]AlF-NOTA-P2-RM26 was compared to that of the  nat Ga-loaded peptide using  125 I-Tyr 4 -BBN as the displacement radioligand. The pharmacokinetics and  in vivo  binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with  18 F within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/µmol). The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [ nat F]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC 50 =4.4±0.8 nM). The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [ 18 F]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p.i. was 5.5±0.7 %ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87±42, 159±47, 38±16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high  in vivo  stability of the Al-F bond. High contrast PET image was obtained 3 h p.i. The initial biological results suggest that [ 18 F]AlF-NOTA-P2-RM26 is a promising candidate for PET imaging of GRPR  in vivo .

In Vitro and In Vivo Evaluation of a 18F-Labeled High Affinity NOTA Conjugated Bombesin Antagonist as a PET Ligand for GRPR-Targeted Tumor Imaging