The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease

Hume, Susan P., Lammertsma, Adriaan A., Myers, Ralph, Rajeswaran, Suren, Bloomfield, Peter M., Ashworth, Sharon, Fricker, Rosemary A., Torres, Eduardo Miguel, Watson, Ian and Jones, Terry 1996. The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. Journal of Neuroscience Methods 67 (2) , pp. 103-112. 10.1016/S0165-0270(96)00010-6

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Abstract

The use of a recently commissioned small-diameter, high-resolution positron emission tomograph (PET) to obtain a measure of specific binding of 3 carbon-11 labelled ligands in rat striatum is described. Using cerebellum as a reference tissue, compartmental modelling was used to obtain individual estimates of striatal binding potential (defined as the ratio of rate constants to and from the specifically bound compartment) for [11C]raclopride (D2 receptors), [11C]SCH 23390 (D1 receptors) and [11C]RTI-121 (dopamine transporter). The coefficients of variation in control, anaesthetized rats were of the order of 10%. Using two models of human disease, namely striatal injection of ibotenic acid to produce postsynaptic cell loss as in Huntington's disease, and 6-hydroxydopamine injection into substantia nigra pars compacta to mimic dopaminergic terminal loss in Parkinson's disease, marked reductions in binding potential were observed for the corresponding pre- or postsynaptic markers. When the regions of interest are so small as to be of the order of the spatial resolution of the system, factors such as spill over and partial volume negate absolute quantification of tissue radioactivity. Nevertheless, the use of PET to monitor relative changes in dopaminergic integrity should be considered as a viable complement to established in vivo microdialysis and post mortem techniques.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Positron emission tomography; Rat; Raclopride; Schering 23390; RTI-121; Fluorodopa; Dopamine receptor; Dopamine transporter.
Publisher:	Elsevier
ISSN:	0165-0270
Last Modified:	23 Mar 2017 05:07
URI:	https://orca.cardiff.ac.uk/id/eprint/66805

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