Development of a simultaneous PET/microdialysis method to identify the optimal dose of 11C-raclopride for small animal imaging
Section snippets
Materials and methods
This work was approved by the BNL IACUC. Forty eight (48) adult male Sprague–Dawley (Taconic Farms, New York) rodents weighing 275–300 g were used for this experiment. All animals were housed and maintained in an AAALAC accredited veterinary facility.
Results
Microdialysis was combined with microPET imaging to establish a range of raclopride mass that decreased 11C-raclopride BP and increased ECF DA. For the microdialysis measures of extracellular DA, our calculated extraction fraction of 0.3 was applied to the measured concentration of DA in the dialysate to correct for the efficiency of the transfer between tissue and probe. Using this correction, our basal levels of extracellular DA varied considerably across animals, with average values of 86.94 ±
Discussion
In the present study, we developed a novel experimental methodology in order to obtain multiple discrete measures of neurotransmitter activity and receptor density using in vivo microdialysis sampling and microPET imaging, respectively, in the same animal. We then applied this approach to independently examine the tolerance of striatal DA systems to increasing mass doses of 11C-raclopride. By combining these two measures, we independently determined the range of influence each measure exerts on
Acknowledgements
We greatly appreciate the tremendous efforts of the BNL Cyclotron (Mike Schueller, Paul Vaska, David Schlyer, Victor Garza, and Frank Zafonte) and assistance provided by Jim Anselmini and Lee Wolcott in the Chemistry Department. We are also grateful for funding support provided by NIH/NIDA in the form of a predoctoral fellowship to W.K.S. (F31-DA15874) and RO1 to S.L.D. (DA015041), and also the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER
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