In Vitro Metabolic Stability and in Vivo 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 in vivo biodistribution in rats. The furoxan ring was labeled with (13)N to follow any nitric oxide release and the 3-methyl substituent was labeled with (11)C to track the metabolite using PET imaging. The in vitro metabolic stability of PRG150 was assessed in rat liver microsomes and compared to in vivo metabolism of the synthesized radiotracers. PET images revealed a higher uptake of (13)N over (11)C 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.
Department of Radiology and Imaging Sciences, Emory University Center for Systems Imaging , Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, Georgia 30329, United States.
Adam B
AB
Pippin
Centre for Integrated Preclinical Drug Development and School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia Campus, Brisbane, Queensland 4072, Australia.
Zaira Hidayah
ZH
Mohd Arshad
Department of Radiology and Imaging Sciences, Emory University Center for Systems Imaging , Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, Georgia 30329, United States.
Ronald J
RJ
Voll
Department of Radiology and Imaging Sciences, Emory University Center for Systems Imaging , Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, Georgia 30329, United States.
Jonathon A
JA
Nye
Centre for Integrated Preclinical Drug Development and School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia Campus, Brisbane, Queensland 4072, Australia.
Sussan
S
Ghassabian
Centre for Integrated Preclinical Drug Development and School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia Campus, Brisbane, Queensland 4072, Australia.
Craig M
CM
Williams
Department of Radiology and Imaging Sciences, Emory University Center for Systems Imaging , Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, Georgia 30329, United States.
Alessandra
A
Mancini
Department of Chemistry, Emory University , 1521 Dickey Drive, Atlanta, Georgia 30322, United States.
Dennis C
DC
Liotta
Centre for Integrated Preclinical Drug Development and School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia Campus, Brisbane, Queensland 4072, Australia.
Maree T
MT
Smith
Department of Radiology and Imaging Sciences, Emory University Center for Systems Imaging , Wesley Woods Health Center, 1841 Clifton Road, NE, Atlanta, Georgia 30329, United States.
Mark M
MM
Goodman
3-methyl-4-furoxancarbaldehyde (PRG150); Furoxan; biodistribution; metabolic stability; nitric oxide (NO); positron emission tomography