title: Synthesis and positron emission tomography evaluation of18F-Glu-Urea-Lys, a prostate-specific membrane antigen-based imaging agent for prostate cancer.
abstract: In recent years, single-photon emission computed tomography and positron emission tomography (PET) have also been used, in addition to computed tomography and magnetic resonance imaging, in targeting the diagnosis of prostate cancer. The aim of this study was to synthesize the prostate-specific membrane antigen (PSMA)-based imaging agent 2-{3-[1-Carboxy-5-(4-[18F] fluoro-benzoylamino)-pentyl]-ureido}-pentanedioic acid (18F-Glu-Urea-Lys, [18F]3) and to detect its PET imaging efficiency for high PSMA expression in prostate cancer. In this study,18F-Glu-Urea-Lys was synthesized in two steps from thep-methoxybenzyl-protected Glu-Urea-Lys precursor usingN-Hydroxysuccinimidyl-4-[18F] fluorobenzoate ([18F]SFB). PET imaging evaluation was conducted in nude mice using LNCaP (PSMA+), and PC-3, 231 and A549 (all PSMA-) xenograft models. The results indicated that18F-Glu-Urea-Lys was produced in radiochemical yields of 28.7%. The radiochemical purity was 99.1% and the mean total synthesis time was 168 min. In nude mice models18F-Glu-Urea-Lys clearly delineated PSMA+LNCaP prostate tumor xenografts on PET imaging. At 4 h post-injection, the contrast agents were only observed in renal, liver, bladder and PSMA+LNCaP tumors. The PSMA-tumor (PC-3, 231 and A549) was clear. In conclusion,18F-Glu-Urea-Lys was found to be easily synthesized. This radiotracer demonstrated high tumor and low-to-normal tissue uptake, fast clearance from non-target tissues and retention in PSMA+prostate tumor xenografts.
authors.affiliation: Graduate School, Dalian Medical University, Dalian, Liaoning 116085, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Graduate School, Dalian Medical University, Dalian, Liaoning 116085, P.R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Graduate School, Dalian Medical University, Dalian, Liaoning 116085, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Xishuang
authors.initials: X
authors.lastname: Song
keywords: 2-{3-[1-Carboxy-5-(4-[18F] fluoro-benzoylamino)-pentyl]-ureido}-pentanedioic acid; positron emission tomography; prostate cancer; prostate-specific membrane antigen