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

Abstract

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 Al(18)F method and the potential of (18)F-Al-NOTA-MATBBN for prostate tumor PET imaging was also evaluated. NOTA-MATBBN was radiolabeled with (18) F using Al(18)F complexes. Partition coefficient, in vitro stability and GRPR binding affinity were also determined. PET studies were performed with (18)F-Al-NOTA-MATBBN in PC-3 tumor-bearing mice. (18)F-Al-NOTA-MATBBN can be produced within 30 min with a decay-corrected yield of 62.5 ± 2.1% and a radiochemical purity of >98%. The logP octanol-water value for the Al(18)F-labeled BBN analog was -2.40 ± 0.07 and the radiotracer was stable in phosphate-buffered saline and human serum for 2 h. The IC50 values of displacement for the (18)F-Al-NOTA-MATBBN with MATBBN was 126.9 ± 2.75 nm. The PC-3 tumors were clearly visible with high contrast after injection of the labeled peptide. At 60 min post-injection, the tumor uptakes for (18)F-Al-NOTA-MATBBN and (18)F-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 (18) F-Al-NOTA-MATBBN was excreted mainly through the kidneys. GRPR-binding specificity was also demonstrated by reduced tumor uptake of (18)F-Al-NOTA-MATBBN after coinjection with excess unlabeled MATBBN peptide at 1 h post-injection. NOTA- MATBBN could be labeled rapidly with (18)F using one step method. (18)F-Al-NOTA-MATBBN may be a promising PET imaging agent for prostate cancer.

• Authors: Donghui Pan, Yongjun Yan, Ronghua Yang, Yu Ping Xu, Fei Chen, Lizhen Wang, Shineng Luo, Min Yang
• Journal: Contrast media & molecular imaging (Contrast Media Mol Imaging) 2014 Sep-Oct Vol. 9 Issue 5 Pg. 342-8 ISSN: 1555-4317 [Electronic] England
• PMID: 24729577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 John Wiley & Sons, Ltd.

Chemical References

• Fluorine Radioisotopes
• Heterocyclic Compounds
• Heterocyclic Compounds, 1-Ring
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid
• Bombesin

Topics

• Animals
• Bombesin (chemistry)
• Cell Line, Tumor
• Fluorine Radioisotopes (chemistry)
• Heterocyclic Compounds (chemistry)
• Heterocyclic Compounds, 1-Ring
• Humans
• Male
• Mice
• Positron-Emission Tomography
• Prostatic Neoplasms (diagnostic imaging, pathology)
• Radiography