PET imaging of prostate tumors with 18F-Al-NOTA-MATBBN

Overexpression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer provides a promising target for detection the disease. MATBBN is a new bombesin analog originating from the GRPR antagonists with a hydrophilic linker. In this study NOTA-conjugated MATBBN was labeled by the (AlF)-F-18 method and the potential of F-18-Al-NOTA-MATBBN for prostate tumor PET imaging was also evaluated. NOTA-MATBBN was radiolabeled with F-18 using (AlF)-F-18 complexes. Partition coefficient, in vitro stability and GRPR binding affinity were also determined. PET studies were performed with F-18-Al-NOTA-MATBBN in PC-3 tumor-bearing mice. F-18-Al-NOTA-MATBBN can be produced within 30min with a decay-corrected yield of 62.5 +/- 2.1% and a radiochemical purity of >98%. The logP octanol-water value for the (AlF)-F-18-labeled BBN analog was -2.40 +/- 0.07 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h. The IC50 values of displacement for the F-18-Al-NOTA-MATBBN with MATBBN was 126.9 +/- 2.75nm. The PC-3 tumors were clearly visible with high contrast after injection of the labeled peptide. At 60min post-injection, the tumor uptakes for F-18-Al-NOTA-MATBBN and F-18-FDG were 4.59 +/- 0.43 and 1.98 +/- 0.35% injected dose/g, and tumor to muscle uptake radios for two tracers were 6.77 +/- 1.10 and 1.78 +/- 0.32, respectively. Dynamic PET revealed that F-18-Al-NOTA-MATBBN was excreted mainly through the kidneys. GRPR-binding specificity was also demonstrated by reduced tumor uptake of F-18-Al-NOTA-MATBBN after coinjection with excess unlabeled MATBBN peptide at 1h post-injection. NOTA- MATBBN could be labeled rapidly with F-18 using one step method. F-18-Al-NOTA-MATBBN may be a promising PET imaging agent for prostate cancer. Copyright (c) 2014 John Wiley & Sons, Ltd.