Synthesis and biological characterization of stable and radioiodinated (+/-)-trans-2-hydroxy-3-P[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM).
The vesamicol analogue (+/-)-trans-2-Hydroxy-3-[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM), a potent ligand for the vesicular acetylcholine transporter (VAChT), was evaluated as a potential radiotracer for studying VAChT density in vivo. In radioligand binding experiments, 3'-IBVM displays subnanomolar affinity for VAChT and 100-fold selectivity for VAChT over sigma1 and sigma2 receptors. Consistent with this profile, radioiodinated (+/-)-3'-IBVM distributed heterogenously in the rat brain following a bolus IV injection, displaying high concentrations in the striatum and moderate to low concentrations in the cortex and cerebellum, respectively. However, co-injection of the radiotracer with the sigma ligand haloperidol resulted in significant reductions of radiotracer levels in all brain regions examined. Therefore, radioiodinated (+/-)-IBVM appears to bind to both VAChT and sigma receptors in vivo.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA. efang001@maroon.tc.umn.edu
von Hohenberg K
Khare
A B
AB
Tu
Z
Z
Mach
R H
RH
Parsons
S M
SM
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D014018:Tissue Distribution; D014101:Torpedo; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
C422187:3'-iodobenzovesamicol; D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008024:Ligands; D026901:Membrane Transport Proteins; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D000109:Acetylcholine