Abstract View
Radiosyntheses of [11C]Carfentanil and [11C]NOP-1A for in-human Opioid Receptor PET Imaging
Category: Carbon-11 Chemistry
Authors:
Enci Ding1, 2,3, Saheed Ayodeji1, 2,3, Joel Bronstein1, 2,3, Otto Muzik2,4, Eric Woodcock5, Huailei Jiang*1, 2,3
1 Cyclotron and Radiochemistry Core, Karmanos Cancer Institute, Detroit, MI, USA
2 PET Center, Karmanos Cancer Institute, Detroit, MI, USA
3 Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA
4 Department of Pediatrics and Neurology, Wayne State University School of Medicine, Detroit, MI, USA
5 Departments of Psychiatry and Behavioral Neurosciences, and of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA
* Mentor: Huailei Jiang, Ph.D
Objective
The μ-opioid receptor (MOR) and nociceptin/orphanin FQ peptide (NOP) receptor are complementary opioid systems involved in pain, addiction, and neuropsychiatric disorders1. Radiotracers targeting these systems, including [11C]Carfentanil ([11C]CFN) for MOR and [11C]NOP-1A for NOP, are important tools for translational neuroimaging. Automated radiosyntheses of [11C]CFN and [11C]NOP-1A with high radiochemical yield and molar activity are essential for successful PET imagings because of their low mass-dose limits and safe human administration. Here, we report the efficient automated radiosynthesis of [11C]CFN and [11C]NOP-1A targeting in-human PET imaging applications.
Methods
Radiosyntheses of [11C]CFN and [11C]NOP-1A were performed with [11C]CH3OTf methylation of their demethyl precursors. [11C]CO2 was generated from a GE PETtrace cyclotron and converted to [11C]CH3OTf on a Synthra MeIPlus Research module. Precursor (1 mg) was dissolved in anhydrous DMSO (200–300 μL) and activated with sodium hydride (4 mg) prior to methylation. After delivery of [11C]CH3OTf into the precursor solution, the reaction mixture was diluted and loaded onto a semi-preparative HPLC column for purification. The desired fraction was collected, diluted and enriched on a solid-phase extraction tC18 cartridge. Followed by sterile water rinsing, [11C]CFN or [11C]NOP-1A was eluted with ethanol, reconstituted in 0.9% NaCl, and sterile-filtered through a 0.22 μm filter. A representative sample was taken for quality control test.
Results
Three validation runs were successfully completed for both [11C]CFN and [11C]NOP-1A. [11C]CFN was yielded in 6.29 ± 0.87 GBq (170 ± 23.4 mCi) at EOS with a total synthesis times of 67 ± 1.5 min. The non-decay-corrected radiochemical yields were 6.75 ± 0.93%, with over 99% radiochemical purity. The nonradioactive masses were 1.26 ± 0.36 μg/mL, and the total chemical impurities were 0.13 ± 0.26 μg/mL. The molar activities at EOS were 182.30 ± 49.51 GBq/μmol (4.93 ± 1.34 Ci/μmol). [11C]NOP-1A was yielded in 8.07 ± 0.78 GBq (218 ± 21.2 mCi) at EOS with a total synthesis time of 60 ± 0.6 min. The non-decay-corrected radiochemical yields were 8.66 ± 0.84%, with over 99% radiochemical purity and total impurities of 3.61 ± 0.14 μg/mL. The formulated [11C]NOP-1A product showed low cold masses (0.35 ± 0.14 μg/mL) and high molar activities of 885.45 ± 0.27 GBq/μmol (23.93 ± 7.17 Ci/μmol) at EOS. All quality control tests passed acceptance criteria according to US Pharmacopeia 823.
Conclusion
High-yield radiosyntheses of [11C]CFN and [11C]NOP-1A were achieved with excellent radiochemical purity, high molar activity. This work enables PET imaging of MOR and NOP receptors in the human brain, facilitating translational investigations of pain, addiction, and neuropsychiatric disease.
Reference
1. Kiguchi N, Ding H, Ko MC. Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse. J Neurosci Res. 2022;100(1):191-202.
Acknowledgment
The Cyclotron and Radiochemistry Core is supported, in part, by NIH Center grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University.
