In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography
| Autor: | Douglas M. Jewett, Richard D. Hichwa, Donald M. Wieland, G.K. Mulholland, Robert A. Koeppe, Bernard W. Agranoff, David E. Kuhl, Richard E. Ehrenkaufer, James E. Carey, Kirk A. Frey |
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| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
medicine.diagnostic_test Chemistry Central nervous system Scopolamine Brain Human brain Pharmacology Ligand (biochemistry) Receptors Muscarinic medicine.anatomical_structure Endocrinology Neurology Positron emission tomography In vivo Cerebral cortex Internal medicine Muscarinic acetylcholine receptor medicine Humans Neurology (clinical) Carbon Radioisotopes Cardiology and Cardiovascular Medicine Receptor Tomography Emission-Computed |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 12(1) |
| ISSN: | 0271-678X |
| Popis: | Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands. |
| Databáze: | OpenAIRE |
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