PET measurement of changes in D2/D3 dopamine receptor binding in a nonhuman primate during chronic deep brain stimulation of the bed nucleus of the stria terminalis.
PET imaging is a powerful tool for measuring physiological changes in the brain during deep brain stimulation (DBS). In this work, we acquired five PET scans using a highly selective D2/D3 dopamine antagonist, 18F-fallypride, to track changes in dopamine receptor availability, as measured by the distribution volume ratio (DVR), through the course of DBS in the bed nucleus of the stria terminalis (BNST) in a nonhuman primate.


METHODS
PET scans were performed on a rhesus monkey with unilateral BNST stimulation during periods of baseline, chronic high frequency (130 Hz) and low frequency (50 Hz) DBS stimulation, and during a washout period between stimulation periods. A final scan was performed with the electrode stimulation starting 110 min into the scan. Whole brain parametric images of (18)F-fallypride DVR were calculated for each condition to track changes in both striatal and extrastriatal D2/D3 availability.


RESULTS
The monkey displayed significant increases in receptor binding throughout the brain during DBS relative to baseline for 130 and 50 Hz, with changes in DVR of: caudate 42%, 51%; putamen 56%, 57%; thalamus 33%, 49%; substantia nigra 29%, 26%; and prefrontal cortex 28%, 56%, respectively. Washout and post-stimulation scans revealed DVR values close to baseline values. Activating the stimulator midway through the final scan resulted in no statistically significant changes in binding.


CONCLUSIONS
PET neuroligand imaging has demonstrated the sensitivity to track changes in dopamine D2/D3 binding during the course of DBS. These methods show great potential for providing insight into the neurochemical consequences of DBS.
Vandehey
Nicholas T
NT
University of Wisconsin-Madison, Department of Medical Physics, United States.
Garell
P Charles
PC
Hampel
Joseph A
JA
Murali
Dhanabalan
D
Smith
Elizabeth M
EM
Davidson
Richard
R
Converse
Alexander K
AK
Nickles
R Jerry
RJ
Christian
Bradley T
BT
D000818:Animals; D001549:Benzamides / Q000378:metabolism; D001703:Biophysics; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D046690:Deep Brain Stimulation / Q000379:methods*; D018492:Dopamine Antagonists / Q000378:metabolism; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011759:Pyrrolidines / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012686:Septal Nuclei / Q000502:physiology*; D013997:Time Factors
D001549:Benzamides; D018492:Dopamine Antagonists; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3