Imaging dopamine receptors in the human brain by positron tomography.

Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.

Design, preparation, and biodistribution of a technetium-99m triaminedithiol complex to assess regional cerebral blood flow.

A new ligand (N-piperidinylethyl-DADT, 5) has been prepared which forms two complexes with 99mTc when stannous chloride is used as a reducing agent for [99mTc] pertechnetate. Biodistribution studies of one of the complexes in mice showed that 2.2% of the injected dose of the tracer was in the brain at 5 min postintravenous injection with 0.53% of the dose remaining in the brain at 30 min postinjection. Brain-to-blood ratios at these times were 5.3 and 3.0, respectively. Biodistribution studies of the other complex showed similar behavior with a slightly lower initial uptake by and faster clearance from the brain. Imaging studies of the more promising of the two complexes were conducted in a monkey and a baboon. In both cases, rapid uptake of the tracer in the brain was observed and clear brain images were obtained. Time-activity curves showed peak uptake in the brain at approximately 5 to 7 min postintravenous injection followed by a plateau of about 11 min. The half-lives for clearance of the tracer from the brains of the monkey and baboon were found to be 63 and 58 min, respectively. These results suggest that this tracer may be useful for brain imaging in humans.

(3,6-Dimethyl-3,6-diazaoctan-1,8-dithiolato-S1,N3,N6,S8)oxotechnetium(V) pertechnetate.

[TcO(C8H18N2S2)]TcO4, Mr = 484.2, monoclinic, P2(1)/c, a = 7.447 (2), b = 16.952 (8), c = 12.236 (3) A, beta = 99.63 (2) degrees, V = 1523 (1) A3, Z = 4, D chi = 2.112, Dm = 2.09 (1) Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.06 mm-1, F(000) = 952, T = 295 (1) K, final R = 0.071 for 2496 significant reflections and 173 parameters. The Tc atom is bound to the oxo group and the N and S atoms of the complex ligand in a rough square pyramid. The Tc atom lies 0.770 (3) A out of the S,N,N',S' plane. This plane is significantly distorted such that N and N' lie nearly 0.25 A out of the plane on opposite sides. The Tc-S bonds [2.238 (3), 2.266 (3) A] are short but other bond lengths and angles are normal.