In vitro binding properties and autoradiographic imaging of 3-iodobenzamide ([125I]-IBZM): a potential imaging ligand for D-2 dopamine receptors in SPECT.
The in vitro binding properties of the [125I] labeled benzamide (S(-)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-hydroxy-3-iodo-6-methoxy- benzamide, IBZM) were determined in bovine and mouse caudate membrane homogenates and by autoradiography of mouse brain slices. [125I]-IBZM binding is saturable and reversible with a Bmax of 373 +/- 51 fmol/mg protein and a Kd of 3.1 +/- 0.62 nM (mean +/- SD, Scatchard analyses) and 0.56 nM as calculated by association and dissociation time constants. In competition experiments, Ki values for the D-2 antagonists YM-09151-2 and spiperone are 4 orders of magnitude lower than the Ki value for the D-1 antagonist SCH-23390 and S(-)-IBZM is ten-fold more potent than R(+)-IBZM. [125I]-IBZM has a low affinity for serotonin S-2 and for alpha receptors. Therefore, it is a highly selective ligand for dopamine D-2 receptors. Autoradiographic images of brain sections incubated with [125I]-IBZM show the dopamine D-2 receptors of the striatum, nucleus accumbens and olfactory tubercle with a high ratio of specific to nonspecific binding. Thus, S(-)-IBZM, when labeled with [123I], may be useful for in vivo imaging of dopamine D-2 receptors by single photon emission computerized tomography (SPECT).
Brücke
T
T
Clinical Brain Imaging Section, National Institute of Mental Health, Bethesda, MD 20892.
Tsai
Y F
YF
McLellan
C
C
Singhanyom
W
W
Kung
H F
HF
Cohen
R M
RM
Chiueh
C C
CC
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002417:Cattle; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D011759:Pyrrolidines / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D001549:Benzamides; D007457:Iodine Radioisotopes; D008024:Ligands; D011759:Pyrrolidines; D011954:Receptors, Dopamine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide