Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain

[ 11 C]Carfentanil ([ 11 C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [ 11 C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [ 11 C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO 2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [ 11 C]CFN PET scans over a wide range of molar activities. Baseline [ 11 C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BP ND ) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained