Dopamine D2 Receptor Imaging with SPECT: Studies in Different Neuropsychiatric Disorders

• Published in: Journal of cerebral blood flow and metabolism 1991-03, Vol.11 (2), p.220-228
• Main Authors: Brücke, T., Podreka, I., Angelberger, P., Wenger, S., Topitz, A., Küfferle, B., Müller, Ch, Deecke, L.
• Format: Article
• Language: English
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; Adult; AGE DEPENDENCE; Aged; Aging - metabolism; AMINES; ANIMALS; Antipsychotic Agents - therapeutic use; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; Benzamides - metabolism; Benzamides - pharmacokinetics; BETA DECAY RADIOISOTOPES; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BODY; BRAIN; Brain Diseases - diagnostic imaging; Brain Diseases - metabolism; CARDIOTONICS; CARDIOVASCULAR AGENTS; CENTRAL NERVOUS SYSTEM; Cerebellum - metabolism; COMPUTERIZED TOMOGRAPHY; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DIAGNOSIS; DIAGNOSTIC TECHNIQUES; DISEASES; DOPAMINE; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; EMISSION COMPUTED TOMOGRAPHY; Frontal Lobe - metabolism; HOURS LIVING RADIOISOTOPES; Humans; Huntington Disease - diagnostic imaging; Huntington Disease - metabolism; HYDROXY COMPOUNDS; INTERMEDIATE MASS NUCLEI; IODINE 123; IODINE ISOTOPES; Iodine Radioisotopes; ISOTOPES; KINETICS; Levodopa - therapeutic use; MAMMALS; MAN; Medical sciences; MEMBRANE PROTEINS; Middle Aged; NERVOUS SYSTEM; NERVOUS SYSTEM DISEASES; Neurology; NEUROREGULATORS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; PATIENTS; PHENOLS; POLYPHENOLS; PRIMATES; PROTEINS; Pyrrolidines - metabolism; Pyrrolidines - pharmacokinetics; RADIOISOTOPES; RADIOLOGY AND NUCLEAR MEDICINE; REACTION KINETICS; RECEPTORS; Receptors, Dopamine - metabolism; Receptors, Dopamine D2; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; Space life sciences; Stereoisomerism; SYMPATHOMIMETICS; Tissue Distribution; TOMOGRAPHY; Tomography, Emission-Computed, Single-Photon; VERTEBRATES
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.1991.53

The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(–)-Iodobenzamide [S-(–)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(–)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 ± 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 ± 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 ± 0.14), but a reduction in L-Dopa-treated cases (1.59 ± 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75–80%. S-(–)-IBZM binding was reduced with increasing age (p < 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding. The results show that dopamine D2 receptors can be clearly visualized with high resolution using the SPECT technique and S-(–)-IBZM as a ligand. A semiquantitative approach can give estimates for receptor blockade or receptor density. This method is of clinical value for the diagnosis of degenerative neurological disorders such as Huntington's disease and for the monitoring of neuroleptic treatment.