RT Journal Article
SR Electronic
T1 Evaluation of <sup>18</sup>F-FA-4 and <sup>11</sup>C-pipzA-4 as Radioligands for the In Vivo Evaluation of the High-Affinity Choline Uptake System
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 269
OP 275
VO 44
IS 2
A1 Christa Gilissen
A1 Tjibbe J. de Groot
A1 Francesca Bronfman
A1 Fred van Leuven
A1 Alfons M. Verbruggen
A1 Guy M. Bormans
YR 2003
UL http://jnm.snmjournals.org/content/44/2/269.abstract
AB 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.