Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [F-18]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [F-18]tetrabutylammonium fluoride ([F-18]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [F-18]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 mm at 37-40 degrees C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18-35% (n = 30, uncorrected) in a 90-mM synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. 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. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radio-nuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [F-18]RSA is an effective blood pool imaging agent in rats and might, as [F-18]HSA, prove similarly useful as a clinical imaging agent. Published by Elsevier Inc