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Naloxone (NLX) is a mu receptor antagonist used to treat acute opioid overdoses. Currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (IN) and 2 mg intramuscular (IM). However, higher mu receptor occupancy (RO) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that have entered the illicit drug market recently. To address this need, a higher dose of NLX has been investigated in a 5 mg IM formulation called ZIMHI but, while the effects of intravenous (IV) and IN administration of NLX on the opioid mu receptor occupancy (RO) have been studied, comparatively little is known about RO for IM administration of NLX. The goal of this study was to examine the effect of IM dosing of NLX on mu RO in rhesus macaques using [ 11 C]carfentanil positron emission tomography (PET) imaging. The lowest dose of NLX (0.06 mg/kg) approximated 51% RO. Higher doses of NLX (0.14 mg/kg, 0.28 mg/kg) resulted in higher mu RO of 70% and 75%, respectively. Plasma levels were 4.6 ng/mL, 16.8 ng/mL, and 43.4 ng/mL for the three IM doses, and a significant correlation between percent RO and plasma NLX level was observed (r = 0.80). These results suggest that higher doses of IM NLX result in higher mu RO and could be useful in combating overdoses resulting from potent synthetic opioids.

[ 11 C]Carfentanil ([ 11 C]CFN) is a selective radiotracer for in vivo positron emission tomography imaging studies of the μ-opioid system that, in our laboratories, is synthesized by methylation of the corresponding carboxylate precursor with [ 11 C]MeOTf, and purified using a C2 solid-phase extraction cartridge. Changes in the commercial availability of common C2 cartridges have necessitated future proofing the synthesis of [ 11 C]CFN to maintain reliable delivery of the radiotracer for clinical imaging studies. An updated synthesis of [ 11 C]CFN is reported that replaces a now obsolete purification cartridge with a new commercially available version and also substitutes the organic solvents used in traditional production methods with ethanol., (Copyright © 2017 John Wiley & Sons, Ltd.)

[11 C]Carfentanil ([11 C]CFN) is a selective radiotracer for in vivo positron emission tomography imaging studies of the μ-opioid system that, in our laboratories, is synthesized by methylation of the corresponding carboxylate precursor with [11 C]MeOTf, and purified using a C2 solid-phase extraction cartridge. Changes in the commercial availability of common C2 cartridges have necessitated future proofing the synthesis of [11 C]CFN to maintain reliable delivery of the radiotracer for clinical imaging studies. An updated synthesis of [11 C]CFN is reported that replaces a now obsolete purification cartridge with a new commercially available version and also substitutes the organic solvents used in traditional production methods with ethanol.