NOVEL TECHNETIUM LIGANDS WITH AFFINITY FOR THE MUSCARINIC CHOLINERGIC RECEPTOR

The synthesis and preliminary biological characterization of two isomeric technetium labeled complexes (2,5,5,9-tetramethyl-4,7-diaza-7-(3' (R)-quinuclidinylcarboxymethyl)-2,9-decanedithiolato oxo (99/99m)technetium(V), [Tc-99/99m]-1 and [Tc-99/99m]-2) designed to exhibit affinity to muscarinic cholinergic receptors are described. In vitro binding assays were conducted in mouse brain homogenates (whore brain-cerebellum) at 37 degrees C by the centrifugation method, where non-specific binding was defined by atropine (1 mu M). The measured affinity (K-D) of [Tc-99]-1 for mAChR was 1.9 +/- 0.5 mu M (mean +/- SEM; n = 3) and [Tc-99]-2 was 4.5 +/- 0.5 mu M (mean +/- SEM; n = 3). Scatchard analysis indicated that B-max values were 10.6 +/- 0.5 and 16.9 +/- 0.5 pmol/mg tissue, respectively. In competition assays, [Tc-99]-1 exhibited an apparent affinity (K-I) of 16.5 mu M (n = 2) against [I-125] iododexetimide, whereas [Tc-99]-2 exhibited an affinity (K-I) of 105 mu M. In vivo, 0.3% of the injected dose of [Tc-99]-1 and [Tc-99m]-2 accumulated in the brain at 5 min after injection. These values indicate technetium analogues of neuroreceptor binding ligands can be synthesized and retain some affinity for the receptor.