Radiochemical Synthesis and Evaluation of ¹³N‑Labeled 5‑Aminolevulinic Acid for PET Imaging of Gliomas

The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported selectivity of 5-ALA, a new positron emission tomography imaging probe was developed by reacting methyl 5-bromolevulinate with [¹³N] ammonia. The radiotracer, [¹³N] 5-ALA, was produced in high radiochemical yield (65%) in 10 min and could be purified using only solid phase cartridges. <i>In vivo</i> testing in rats bearing intracranial 9L glioblastoma showed peak tumor uptake occurred within 10 min of radiotracer administration. Immunohistochemical staining and fluorescent imaging was used to confirm the tumor location and accumulation of the tracer seen from the PET images. The quick synthesis and rapid tumor specific uptake of [¹³N] 5-ALA makes it a potential novel clinical applicable radiotracer for detecting and monitoring tumors noninvasively

<i>In Vitro</i> Metabolic Stability and <i>in Vivo</i> Biodistribution of 3‑Methyl-4-furoxancarbaldehyde Using PET Imaging in Rats

Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is currently difficult to treat using clinically available analgesics. Recent work suggests a progressive depletion of nitric oxide (NO) in nerve cells may be responsible for the pathobiology of PDN. The nitric oxide donor, 3-methyl-4-furoxancarbaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of PDN. To gain insight into the mechanism of analgesia, methods to radiolabel PRG150 were developed to assess the <i>in vivo</i> biodistribution in rats. The furoxan ring was labeled with ¹³N to follow any nitric oxide release and the 3-methyl substituent was labeled with ¹¹C to track the metabolite using PET imaging. The <i>in vitro</i> metabolic stability of PRG150 was assessed in rat liver microsomes and compared to <i>in vivo</i> metabolism of the synthesized radiotracers. PET images revealed a higher uptake of ¹³N over ¹¹C radioactivity in the spinal cord. The differences in radioactive uptake could indicate that a NO release in the spinal cord and other components of the somatosensory nervous system may be responsible for the analgesic effects of PRG150 seen in the rat model of PDN