PT  - JOURNAL ARTICLE
AU  - Andrea Bettio
AU  - Michael Honer
AU  - Cristina Müller
AU  - Matthias Brühlmeier
AU  - Ursina Müller
AU  - Roger Schibli
AU  - Viola Groehn
AU  - August P. Schubiger
AU  - Simon M. Ametamey
TI  - Synthesis and Preclinical Evaluation of a Folic Acid Derivative Labeled with <sup>18</sup>F for PET Imaging of Folate Receptor–Positive Tumors
DP  - 2006 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1153--1160
VI  - 47
IP  - 7
4099  - http://jnm.snmjournals.org/content/47/7/1153.short
4100  - http://jnm.snmjournals.org/content/47/7/1153.full
SO  - J Nucl Med2006 Jul 01; 47
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.