The use of [18F]4-fluorobenzyl iodide (FBI) in PET radiotracer synthesis: model alkylation studies and its application in the design of dopamine D1 and D2 receptor-based imaging agents.
[18F]4-Fluorobenzyl iodide ([18F]FBI) was prepared, and a series of model alkylation studies were conducted to determine its chemical reactivity toward nitrogen and sulfur nucleophiles of varying nucleophilicities. [18F]FBI was found to react rapidly with secondary amines and anilines to give the corresponding N-[18F]4-fluorobenzyl analogue in high yield. Amides and thiol groups required the use of a base catalyst. The utility of [18F]FBI was documented by investigation of dopamine D1 and D2 receptor-based radiotracers.
Mach
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RH
Cerebrovascular Research Center, University of Pennsylvania, Philadelphia 19104-6063.
Elder
S T
ST
Morton
T E
TE
Nowak
P A
PA
Evora
P H
PH
Scripko
J G
JG
Luedtke
R R
RR
Unsworth
C D
CD
Filtz
T
T
Rao
A V
AV
D000478:Alkylation; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis; D001552:Benzazepines / Q000138:chemical synthesis; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry; D014055:Tomography, Emission-Computed
D001549:Benzamides; D001552:Benzazepines; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D010880:Piperidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C083673:fluoroclebopride; C083674:7-chloro-8-hydroxy-1-(4'-(4-fluorobenzyl)thiophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine; C083672:4-fluorobenzyl iodide; D013455:Sulfur; D009584:Nitrogen