Retardation of 17-oxidation of 16 alpha-[18F]fluoroestradiol-17 beta by substitution of deuterium for hydrogen in the 17 alpha position(6).
We describe the synthesis, in vitro metabolism and biodistribution of [17 alpha-2H]16 alpha-[18F]fluoroestradiol ([18F]DFES). The clinically useful breast cancer imaging agent, 16 alpha-[18F]fluoroestradiol-17 beta ([18F]FES), was deuterated at the C-17 alpha position to lower the rate of C-17 alcohol oxidation. Metabolism studies in immature female rat and mature female baboon isolated hepatocytes showed [18F]DFES being consumed ca. 2.5 times slower than [18F]FES. Biodistribution studies and time-activity curve measurements in female rats showed [18F]DFES to have superior uptake characteristics compared to [18F]FES for imaging estrogen-receptor rich targets.
Bonasera
T A
TA
Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Jonson
S D
SD
Pajeau
T S
TS
Katzenellenbogen
J A
JA
Welch
M J
MJ
D000375:Aging / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D003903:Deuterium / Q000737:chemistry; D004031:Diestrus / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D006859:Hydrogen / Q000737:chemistry; D007553:Isotope Labeling; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D010215:Papio; D051381:Rats; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D004958:Estradiol; D006859:Hydrogen; C043436:16-fluoroestradiol; D003903:Deuterium