Kan Sam Lee

Tourette Syndrome: Prediction of Phenotypic Variation in Monozygotic Twins by Caudate Nucleus D2 Receptor Binding

Tourette syndrome, a chronic tic disorder with autosomal dominant inheritance, exhibits considerable phenotypic variability even within monozygotic twin pairs. The origins of this variability remain unclear. Recent findings have implicated the caudate nucleus as a locus of pathology, and pharmacological evidence supports dopaminergic involvement. Within monozygotic twins discordant for Tourette syndrome severity, differences in D2 dopamine receptor binding in the head of the caudate nucleus predicted differences in phenotypic severity (r = 0.99); this relation was not observed in putamen. These data may link Tourette syndrome with a spectrum of neuropsychiatric disorders that involve associative striatal circuitry.

Radiosynthesis and preliminary evaluation of 5-[123/125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine: a radioligand for nicotinic acetylcholine receptors

The radiochemical syntheses of 5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5-[123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)metho xy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/mumol, respectively. Binding affinities of [125I]1 and [123I]1 in vitro (rat brain membranes) were each characterized by a Kd value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.

Analysis of the metabolites of [I-123]β-CIT in plasma of human and nonhuman primates

[I‐123]β‐CIT is a single photon emission computed tomography (SPECT) radioligand that has been used for in vivo studies of the dopamine and serotonin transporters. Two metabolite peaks of β‐CIT have been observed by high performance liquid chromatography (HPLC), but neither has been chemically identified. One major metabolite is clearly hydrophilic. Previous reports have not agreed on the amount of the second metabolite and the extent to which it may cross the blood‐brain barrier. To clarify this controversy, we have studied β‐CIT metabolites using a protein precipitation method and an organic extraction method followed by HPLC separation. Plasma from both human and nonhuman (rhesus) primates was analyzed. Concentrations of the second metabolite were substantially lower in rhesus than in human for nearly equal parent concentrations. Furthermore, in rhesus the second metabolite is partially soluble in the organic solvent ethyl acetate, whereas in human it is essentially insoluble. These observations account for the contradictions in the literature. The hydrophilic nature of the human metabolite renders it unlikely that it crosses the blood‐brain barrier in sufficient quantities to interfere with the quantitative assessment of dopamine transporter densities. Synapse 25:306–308, 1997.