Quantitation of Carbon‐11‐labeled raclopride in rat striatum using positron emission tomography

Synapse - Tập 12 Số 1 - Trang 47-54 - 1992
Susan P. Hume1, R. Myers1, P Bloomfield1, Jolanta Opacka‐Juffry1, Jill E. Cremer1, R. G. Ahier1, SK Luthra1, David J. Brooks1, Adriaan A. Lammertsma1
1MRC Cyclotron Unit, Hammersmith Hospital, London W12 OHS, England

Tóm tắt

AbstractUsing conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11C] raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters.Carbon‐11‐labeled raclopride was given i. v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time‐activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite‐corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from “free to bound” and “bound to free” compartments, was of the order of 0.6. This was reduced threefold by predosing with nonraioactive raclopride. Increasing extracellular dopamine levels by predosing with d ‐amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with γ‐butyrolactone caused a significant increase.Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time‐activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data.

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Tài liệu tham khảo

10.1007/BF00280072

10.1016/0301-0082(90)90027-E

10.1111/j.1471-4159.1988.tb02919.x

10.1016/0006-8993(89)90118-2

Carson E. R., 1986, Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart, 347

Cherry S. R., 1991, Physical evaluation of an animal tomograph for PET, J. Cereb. Blood Flow Metab., 11, S567

10.1038/jcbfm.1991.1

10.1002/syn.890070409

10.1038/jcbfm.1989.98

10.1007/BF00212840

10.1001/archpsyc.1990.01810150013003

10.1038/jcbfm.1989.59

Gjedde A., 1991, Dopamine D2 receptors in schizophrenia: hypothetical reconciliation of PET results, J. Cereb. Blood Flow Metab., 11, S824

10.1111/j.1471-4159.1990.tb05794.x

10.1038/jcbfm.1991.157

10.1007/BF01244652

10.1016/0006-2952(85)90778-6

10.1038/jcbfm.1991.103

10.1109/23.289374

10.1002/syn.890060113

10.1002/syn.890070210

Paxinos G., 1986, The Rat Brain in Streotaxic Coordinates

Rajeswaran S. Bailey D. L. Hume S. P. Townsend D. W. Geiss bühler A. Young J. andJones T.(1991a)2D and 3D Imaging of small animals and the human radial artery with a high resolution block detector for PET. IEEE Trans. Med. Imaging in press.

10.1016/0165-0270(91)90071-7

10.1007/BF00169199

Robb R. A. andBarillot C.(1988)Interacitive 3‐D image display and analysis. In: Proceedings of the SPIE Technical Symposium on Optics Electro‐Optics and Sensors Orlando Florida.

10.1016/0006-8993(91)90995-8

10.1002/syn.890030113

10.1001/archpsyc.1990.01810240090014

Spinks T. J. Jones T. Bailey D. L. Townsend D. W. Grootoonk S. Bloomfied P. M. Gilardi M. ‐C. Casey M. E. Sipe B. andReed J.(1992)Physical performance of a positron tomograph for brain imaging with retractable septa. Phys. Med. Biol. in press.

10.1016/0165-0173(90)90015-G

10.1126/science.2878495

10.1109/23.106682

10.1002/syn.890090305

10.1111/j.1471-4159.1983.tb00893.x

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Synapse

Tập 12 Số 1

47-54

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