title: Development of a new thiol site-specific prosthetic group and its conjugation with [Cys(40)]-exendin-4 for in vivo targeting of insulinomas.
abstract: A new tracer, N-5-[(18)F]fluoropentylmaleimide ([(18)F]FPenM), for site-specific labeling of free thiol group in proteins and peptides was developed. The tracer was synthesized in three steps ((18)F displacement of the aliphatic tosylate, di-Boc removal by TFA to expose free amine, and incorporation of the free amine into a maleimide). The radiosynthesis was completed in 110 min with 11-17% radiochemical yield (uncorrected), and specific activity of 20-49 GBq/μmol. [(18)F]FPenM showed comparable labeling efficiency with N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM). Its application was demonstrated by conjugation with glucagon-like peptide type 1 (GLP-1) analogue [cys(40)]-exendin-4. The cell uptake, binding affinity, imaging properties, biodistribution, and metabolic stability of the radiolabeled [(18)F]FPenM-[cys(40)]-exendin-4 were studied using INS-1 tumor cells and INS-1 xenograft model. Positron emission tomography (PET) results showed that the new thiol-specific tracer, [(18)F]FPenM-[cys(40)]-exendin-4, had high tumor uptake (20.32 ± 4.36%ID/g at 60 min postinjection) and rapid liver and kidney clearance, which was comparable to the imaging results with [(18)F]FBEM-[cys(40)]-exendin-4 reported by our group.
authors.affiliation: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), 31 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Yue
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Jinxia
authors.initials: J
authors.lastname: Guo
authors.forename: Zhongchan
authors.initials: Z
authors.lastname: Sun
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry*; D000077270:Exenatide; D005260:Female; D007340:Insulinoma / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014018:Tissue Distribution; D014688:Venoms / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D010455:Peptides; D013438:Sulfhydryl Compounds; D014688:Venoms; D000077270:Exenatide; D003545:Cysteine