Synthesis and Preclinical Evaluation of a Folic Acid Derivative Labeled with 18F for PET Imaging of Folate Receptor–Positive Tumors

Journal of Nuclear Medicine

Andrea Bettio¹  Michael Honer¹  Simon M. Ametamey¹  Ursina Müller¹  Matthias Brühlmeier¹  Viola Groehn¹  August P. Schubiger¹  Roger Schibli¹  Cristina Müller¹ 

关键词: folate receptor;    ¹⁸F labeling;    PET;    tumor imaging;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown