Comparison of [ 11 C]Diprenorphine and [ 11 C]Carfentanil Binding to Opiate Receptors in Humans by Positron Emission Tomography

The kinetics and regional distribution of [¹¹C]carfentanil, a μ-selective opiate receptor agonist, and [¹¹C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [¹¹C]diprenorphine than [¹¹C]carfentanil in all regions. [¹¹C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at ∼40 min, whereas [¹¹C]diprenorphine showed a linear increase until ∼60 min. Kinetics of specific binding demonstrated significant dissociation of [¹¹C]carfentanil from opiate receptors, whereas little dissociation of [¹¹C]diprenorphine was observed during the 90-min scan session. Regional distributions of [¹¹C]carfentanil and [¹¹C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of μ-receptors), [¹¹C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [¹¹C]carfentanil, consistent with labeling of additional, non-μ sites by [¹¹C]diprenorphine. We conclude from these studies that [¹¹C]diprenorphine labels other opiate receptor subtypes in addition to the μ sites selectively labeled by [¹¹C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the δ- and κ-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace μ, δ, and κ subtypes, will help offset these limitations.