title: 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.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Pan
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.forename: Yu Ping
authors.initials: YP
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.forename: Shineng
authors.initials: S
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry*; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011859:Radiography
chemical_list: D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D001839:Bombesin
keywords: 18F; PET; bombesin; fluoride-aluminum chelate; prostate cancer