Evaluation of 18F-FA-4 and 11C-pipzA-4 as Radioligands for the In Vivo Evaluation of the High-Affinity Choline Uptake System

Journal of Nuclear Medicine

Alfons M. Verbruggen¹  Fred van Leuven¹  Francesca Bronfman¹  Christa Gilissen¹  Tjibbe J. de Groot¹  Guy M. Bormans¹ 

关键词: PET;    high-affinity choline uptake;    ¹⁸F;    ¹¹C;    radiopharmaceutical;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

4,4′-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system. We have evaluated 4-[1-hydroxy-2-(4-18F-fluoromethylpiperidin-1-yl)ethyl]-4′-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl (18F-FA-4) and 4-[1-hydroxy-2-(4-11C-methylpiperazin-1-yl)ethyl]-4′-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl (11C-pipzA-4), an 18F- and a 11C-labeled derivative of A-4 as potential in vivo tracers for the HACU system. Methods: The biodistribution of both compounds was determined in mice, and the intracerebral distribution was visualized by ex vivo and in vitro autoradiography. The in vitro affinity of the compounds was determined by a displacement study with 3H-HC-3 on mice brain slices. Results: In mice, both tracers show a high and persistent brain uptake. In vitro autoradiography shows binding to the striatum, whereas ex vivo autoradiography shows homogeneous binding throughout the brain. FA-4 and pipzA-4 inhibited the 3H-HC-3 binding with a 50% inhibitory concentration of 57 nmol/L and 320 nmol/L, respectively. Conclusion: The evaluated compounds have affinity for HACU and show high uptake in the brain. In vitro binding of the compounds to the striatum cannot be inhibited by the presence of HC-3, whereas binding of HC-3 was inhibited by the presence of both FA-4 and pipzA-4, suggesting allosteric binding.

【 授权许可】

Unknown