The in vitro dissociation kinetics of (R,R)-[125I]4IQNB is reflected in the in vivo washout of the radioligand from rat brain.
We have determined the kinetics of dissociation of (R)-3-Quinuclidinyl (R)-4-[125I]Iodobenzilate ((R,R)-[125I]4IQNB) from muscarinic acetylcholine receptor preparations from the cortex, hippocampus, caudate/putamen, thalamus, pons and colliculate bodies. The dissociation curves are well described by a biexponential function and are consistent with subtype selectivity favoring slow dissociation from the M1, M3, and M4 receptors with a 20-fold faster dissociation rate for the M2 receptor. Following intravenous injection, (R,R)-[125I]4IQNB binds to receptor in the rat brain in concentrations which reflect the receptor concentration present in a structure. We determined the extent of radioligand present at two times, 2 and 24 hrs, as an indication of the relative proportions of m-AChR which exhibits rapid vs. slow dissociation of (R,R)-[125I]4IQNB. A good correlation between in vitro and in vivo results suggests that the relative populations of receptor subtypes can be imaged using in vivo pharmacokinetics of (R,R)-[125I]4IQNB.
Gibson
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RE
Department of Radiology, George Washington University Medical Center, Washington, D.C. 20037.
Moody
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T
Schneidau
T A
TA
Jagoda
E M
EM
Reba
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RC
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism
D011976:Receptors, Muscarinic; C028484:quinuclidinyl benzilate receptor; D011813:Quinuclidinyl Benzilate; C040062:3-quinuclidinyl-4-iodobenzilate