[¹¹C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

Abstract 

Introduction

Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice.

Methods

[¹¹C]-MeJDTic was prepared by methylation of JDTic with [¹¹C]-methyl triflate. The binding of [¹¹C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice.

Results

[¹¹C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [¹¹C]-MeJDTic rapidly crossed the blood–brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor.

Conclusion

These findings suggested that [¹¹C]-MeJDTic appeared to be a promising selective “lead” radioligand for κ-opioid receptor PET imaging.

Keywords: Carbon-11, Positron emission tomography, Kappa receptor, Mouse, MeJDTic