HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perlmutter, J. S. Articles by Welch, M. J. Search for Related Content PubMed PubMed Citation Articles by Perlmutter, J. S. Articles by Welch, M. J.

MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans

From the Department of Neurology and Neurological Surgery (Neurology) (Dra. Perlmutter and Raichle), Malinckrodt Institute of Radiology (Radiation Sciences) (Drs. Perlmutter, Kilbourn, Raichle, and Welch), and the McDonnell Center for the Study of High Brain Function (Dr. Raichle), Washington University School of Medicine, St. Louis, MO.

We measured in vivo dopaminergic receptor binding usingpositron emission tomography and ¹⁸F-spiperone in an untreated symptomatic subject with MPTP-induced parkinsonism. Our technique determines four variables related to entry of ¹⁸F-spiperone into brain tissue and subsequent binding to receptors: (1) the combined forward-rate constant k₁' (equal to the product of the maximum number of available specific binding sites, B_max, times the association rate constant [k_a] of ¹⁸F-spiperone and receptor); (2) the binding site dissociation rate constant k_–1; (3) the free fraction of radioligand not specifically bound in brain tissue, f₂; and (4) the regional permeability-surface-area product (PS) of the blood-brain barrier for spiperone. PS and f₂ in the patient were not different from that of 10 normal volunteers, whereas the combined forward-rate constant (left caudate: k₁' = 67.6 sec^–l, normal = 0.140 ± 0.056) and the dissociation rate constant (left caudate: k_–1 = 0.116 sec^–1, normal = 0.000339 ± 0.000149) were elevated. These findings provide potential new insights not only into the pathophysiology of this disease but into the clinical importance of dopamine receptor function as well.

Address correspondence and reprint requests to Dr. Perlmutter, Division of Radiation Sciences, Barnes Hospital Plaza, Box 8131,510 South Kingshighway Boulevard, St. Louis, MO 63110.

Supported by NIH grants NS06833, HL13851, Teacher Investigator Development Award NS00929 (J.S.P.) and the Greater St. Louis Chapter of the American Parkinson's Disease Association.

Received March 5, 1987. Accepted for publication in final form July 23, 1987.

This article has been cited by other articles:

				G. Grunder, A. Carlsson, and D. F. Wong Mechanism of New Antipsychotic Medications: Occupancy Is Not Just Antagonism Arch Gen Psychiatry, October 1, 2003; 60(10): 974 - 977. [Abstract] [Full Text] [PDF]

				J. S. Perlmutter, M. K. Stambuk, J. Markham, K. J. Black, L. McGee-Minnich, J. Jankovic, and S. M. Moerlein Decreased [18F]Spiperone Binding in Putamen in Idiopathic Focal Dystonia J. Neurosci., January 15, 1997; 17(2): 843 - 850. [Abstract] [Full Text] [PDF]