Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging. (7th March 2019)

• Record Type: Journal Article
• Authors: Huang, Shun; Li, Hongsheng; Han, Yanjiang; Fu, Lilan; Ren, Yunyan; Zhang, Yin; Li, Youcai; Sun, Penghui; Wang, Meng; Wu, Hubing; Wang, Quanshi; Hu, Kongzhen
• Other Names: Vali Reza Academic Editor.
• Is Part Of: Contrast media & molecular imaging. Volume 2019(2019)
• Publication Date: 2019-03-07
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1155/2019/5635269
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an 18 F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu 1 -His 2 -Trp 3 -Ser 4 -Tyr 5 -Gly 6 -Leu 7 -Arg 8 -Pro 9 -Gly 10 -NH2 ) peptide analogues FP-d -Lys 6 -GnRH (FP = 2-fluoropropanoyl) and NOTA-P-d -Lys 6 -GnRH ( P = ethylene glycol) were designed and synthesized. The IC50 values of FP-d -Lys 6 -GnRH and NOTA-P-d -Lys 6 -GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[ 18 F]fluoropropionate was conjugated to the ε -amino group of thed -lysine side chain ofd -Lys 6 -GnRH to yield the new tracer [ 18 F]FP-d -Lys 6 -GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20−100 GBq/ µ mol (n = 6 ). Cell uptake studies of [ 18 F]FP-d -Lys 6 -GnRH in GnRH receptor-positive PC-3 cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [ 18 F]FP-d -Lys 6 -GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [ 18 F]FP-d -Lys 6 -GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. The presented results indicated a potential of the novel tracer [ 18 F]FP-d -Lys 6 -GnRH for tumor GnRH receptor imaging.