RT Journal Article SR Electronic T1 Synthesis and Preclinical Evaluation of a Folic Acid Derivative Labeled with 18F for PET Imaging of Folate Receptor–Positive Tumors JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1153 OP 1160 VO 47 IS 7 A1 Andrea Bettio A1 Michael Honer A1 Cristina Müller A1 Matthias Brühlmeier A1 Ursina Müller A1 Roger Schibli A1 Viola Groehn A1 August P. Schubiger A1 Simon M. Ametamey YR 2006 UL http://jnm.snmjournals.org/content/47/7/1153.abstract AB Folic acid was linked regioselectively through its α- and γ-carboxyl groups to 4-fluorobenzylamine (FBA), and the α- and γ-FBA-folate regioisomers were evaluated for their ability to bind to folate receptor–positive cells. The 18F-labeled α/γ-FBA-folate counterpart was examined for in vivo tumor targeting efficiency in nude mice bearing folate receptor–positive tumor cells. Methods: 18F-α/γ-FBA-folate was prepared in a 4-step reaction sequence starting from folic acid. The relative binding affinities of the α- and γ-FBA-folates to the folate receptor with respect to parent folic acid were determined in cultured KB-31 cells (nasopharyngeal epidermal carcinoma cell line) overexpressing the folate receptor using 3H-folic acid. Tumor accumulation of the 18F-labeled α/γ-FBA-folate and 18F-FDG was analyzed in vivo by high-resolution PET. Biodistribution and PET studies were performed under baseline and blockage conditions. Results: The radiochemical yield of the coupling step ranged from 15% to 44%, and the maximum specific radioactivity was 24 GBq/μmol. The in vitro binding affinities of the α- and γ-isomers and folic acid were 71, 62, and 41 nmol/L, respectively. PET revealed heterogeneous uptake of the radioligand, with the highest activity concentrations found in the tumor rim. In contrast, 18F-FDG uptake in a nude mouse bearing KB-31 folate receptor–positive tumors was negligible. Radioligand uptake in tumors at 125 min after injection amounted to 6.56% of the injected dose per gram of tissue (%ID/g) in control animals, whereas radioactivity accumulation in the tumors of folic acid–treated animals was significantly reduced by more than 80%—to 1.07 %ID/g (P = 0.001). Conclusion: This new 18F-labeled folic acid derivative is a promising tool for PET imaging of folate receptor–positive tumors.