title: Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging.
abstract: 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, [(18)F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [(18)F]tetrabutylammonium fluoride ([(18)F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [(18)F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH9) for 15 min at 37-40 °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-min 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 radionuclide, 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 [(18)F]RSA is an effective blood pool imaging agent in rats and might, as [(18)F]HSA, prove similarly useful as a clinical imaging agent.
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD. Electronic address: bhattacharyyaf@mail.nih.gov.
authors.forename: Falguni
authors.initials: F
authors.lastname: Basuli
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD.
authors.forename: Changhui
authors.initials: C
authors.lastname: Li
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD.
authors.forename: Biying
authors.initials: B
authors.lastname: Xu
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Coble
authors.affiliation: Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD.
authors.forename: Olga
authors.initials: O
authors.lastname: Vasalatiy
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD; Contractor to Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), NCI-Frederick, Frederick, MD, 21702, United States.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD; Contractor to Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), NCI-Frederick, Frederick, MD, 21702, United States.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Green
authors.affiliation: Clinical Research Directorate/CMRP, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Griffiths
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Jagoda
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D015637:Gated Blood-Pool Imaging / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D009525:Niacin / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D012709:Serum Albumin / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D012709:Serum Albumin; D009525:Niacin
keywords: Blood pool imaging; PET; [(18)F]albumin