Facile fluorine-18 labeling of serum albumins via the coupling of [18F]fluoronicotinic acid tetrafluorophenyl ester with albumin amine groups

Authors

• F Basuli
• B Xu
• O Vasalatiy
• GL Griffiths
• E Jagoda
• M Green
• J Seidel
• P Choyke
• R Swenson

Abstract

Our objective is to develop an improved, optimized, simple, reproducible and clinically translatable method to label serum albumins with fluorine-18 for use as a blood pool imaging agent. Fluorine-18 labeling of albumin was achieved by an indirect method. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester was prepared first by the reaction of its quaternary ammonium triflate precursor with [18F]TBAF according to a literature method, with modifications. Final conjugation of the serum albumin with [18F] fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester in phosphate buffer, pH 9, for 20 min produced fluorine-18-radiolabeled albumins (rat & human). Purification of the products was done using a mini-PD MiniTrap G-25 column. The conjugation yield was 92-98% within 20 min at 37-40 οC. The overall radiochemical yield of the reaction was 18-35% (n= 30, uncorrected) in a 90 minute radiolabeling time. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. Fluorine-18 labeling of serum albumins was successfully accomplished with a moderate overall radiochemical yield in a 90 minute synthesis time. No time consuming HPLC purifications of intermediates or products are required with this method. These preclinical biodistribution and PET imaging results indicate that [18F]RSA is an effective blood pool imaging agent in rats and might, as [18F]HSA, prove similarly useful as a clinical imaging agent.

Scientific Focus Area: Research Support Services

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