Stereoselective synthesis and biological evaluation of syn-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid as a potential positron emission tomography brain tumor imaging agent.
Amino acid syn-1-amino-3-fluoro-cyclobutyl-1-carboxylic acid (syn-FACBC) 12, the isomer of anti-FACBC, has been selectively synthesized and [(18)F] radiofluorinated in 52% decay-corrected yield using no-carrier-added [(18)F]fluoride. The key step in the synthesis of the desired isomer involved stereoselective reduction using lithium alkylborohydride/zinc chloride, which improved the ratio of anti-alcohol to syn-alcohol from 17:83 to 97:3. syn-FACBC 12 entered rat 9L gliosarcoma cells primarily via L-type amino acid transport in vitro with high uptake of 16% injected dose per 5 x 10(5) cells. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated high tumor to brain ratio of 12:1 at 30 min post injection. In this model, amino acid syn-[(18)F]FACBC 12 is a promising metabolically based radiotracer for positron emission tomography brain tumor imaging.
Yu
Weiping
W
Department of Radiology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Williams
Larry
L
Camp
Vernon M
VM
Malveaux
Eugene
E
Olson
Jeffrey J
JJ
Goodman
Mark M
MM
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D007553:Isotope Labeling; D009795:Octanes / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D013237:Stereoisomerism
D000596:Amino Acids; D002264:Carboxylic Acids; D009795:Octanes; D019275:Radiopharmaceuticals; C540836:syn-1-amino-3-(18F)fluorocyclobutyl-1-carboxylic acid