[(18)F]Fluoropyruvate: radiosynthesis and initial biological evaluation.
The radiosynthesis of [(18)F]fluoropyruvate was investigated using numerous precursors were synthesized from ethyl 2,2-diethoxy-3-hydroxypropanoate (5) containing different leaving groups: mesylate, tosylate, triflate, and nonaflate. These precursors were evaluated for [(18)F]fluoride incorporation with triflate being superior. The subsequent hydrolysis step was investigated, and an acidic hydrolysis was optimized. After establishing suitable purification and formulation methods, the [(18)F]fluoropyruvate could be isolated in ca. 50% d.c. yield. The [(18)F]fluoropyruvate was evaluated in vitro for its uptake into tumor cells using adenocarcinomic human alveolar basal epithelial cells (A549) and unfortunately showed an uptake of approximately 0.1% of the applied dose per 100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in vivo using nude mice showed a high degree of bone uptake from defluorination, which will limit its potential as an imaging agent for metabolic processes.
Bayer Healthcare, Global Drug Discovery, Müllerstrasse 178, 13353, Berlin, Germany.
Keith
K
Graham
Andre
A
Müller
Lutz
L
Lehmann
Norman
N
Koglin
Ludger
L
Dinkelborg
Holger
H
Siebeneicher
D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D054879:Halogenation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011773:Pyruvates / Q000138:chemical synthesis / Q000737:chemistry*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D014057:Tomography, X-Ray Computed
D005462:Fluorine Radioisotopes; D011773:Pyruvates; D019275:Radiopharmaceuticals; C017319:3-fluoropyruvate
PET imaging; fluorine-18 radiolabeling; fluoropyruvate; pyruvate dehydrogenase; pyruvate kinase