In vivo biodistribution of the nitric oxide donor, PRG150, using PET imaging in rats.

Objectives The nitric oxide donor, 3-methyl-4-furoxanaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of painful diabetic neuropathy (PDN). To gain insight into the mechanism of analgesia, methods to radiolabeled PRG150 were developed to assess the in vivo biodistribution in rats using PET imaging.

Methods Radiolabeling of [N-13] PRG150 was achieved in a good radiochemical yield (34 ± 2%) by nitrating crotonaldehyde with carrier-added [N-13] nitrite in acetic acid. To follow the carbon based metabolite for a comparison, [C-11] PRG150 was synthesized via Suzuki cross coupling of a pinacolboronate ester with [C-11] methyl iodide to furnish [C-11] diethoxy crotonaldehyde in situ. Using nitrous acid to furnish the furoxan ring, [C-11] PRG150 was made in moderate radiochemical yield (21 ± 8%). PET imaging and biodistribution studies of both tracers were conducted in male Sprague Dawley rats.

Results MicroPET images and time-activity plots show major uptake of both N-13 and C-11 tracers in the cardiovascular system, liver, kidneys, and bladder. A comparison of the radioactivity elimination in the spine revealed a higher peak uptake [N-13] PRG150 compared to [C-11] PRG150. Subcutaneous administration of [C-11] PRG150 resulted in a delayed peak uptake in the spine, which correlates well with the onset of analgesia seen in the rat model of PDN.

Conclusions The differences in [N-13] and [C-11] radioactive uptake could indicate NO release at multiple levels of the somatosensory nervous system.