Comparative PET imaging of D2/D3 receptors in the rodent spinal cord with [¹⁸F]fallypride and [¹¹C]fallypride

Objectives Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands ¹⁸F-falllypride and ¹¹C-fallypride.

Methods Male Sprague-Dawley rats were used in all studies. For in vivo studies two different animals received a 150-min ¹⁸F-fallypride scan and a 90-min ¹¹C-Fallypride scan using a Siemens Inveon dedicated PET scanner. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo for 30-min. Further, the spine was then sectioned and analyzed in vitro using a Cyclone Phosphor Imager. Binding of radiotracer in the spinal cord (SC) was calculated relative to binding in the striatum (STR). Regions of interest (ROI) were drawn over the STR, cerebellum and two areas of the SC (lower and upper). For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis.

Results In Vitro studies showed ¹⁸F-fallypride binding of 77.4% in the upper spinal cord and 89.8% in the lower spinal cord. In Vivo analysis yielded BP values of 4.2 (upper and lower SC) and 17.8 for the STR. For ¹¹C-fallypride the values were 8.63 in the STR and 0.6 in the SC. Relative to striatum, ex vivo studies showed ¹⁸F-fallypride binding of 1.21% in the lower spinal cord, 1.15% in the upper spinal cord, and 1.07% for the total spinal cord. ¹¹C Fallypride showed binding of 9.00% in the lower SC, 8.96% in the upper SC, and 9.24% for the total spinal cord.

Conclusions Our micro PET studies showed quantifiable ¹⁸F-Fallypride and ¹¹F-Fallypride binding in the spinal cord in vivo. Increased uptake was observed near sites of the various plexuses (lumbar/cervical). The binding pattern correlates well with lower extremity nerves and may suggest a possible use of D2/D3 receptor to study the restless leg syndrome. ¹¹C-fallypride also showed reduced bone uptake compared to the ¹⁸F-fallypride.

Research Support NIH R01 EB00611