Total-body [¹¹C]carfentanil PET: Liver-brain axis in methadone vs. buprenorphine treatment.

Abstract

To examine the relationship between brain mu opioid receptor (MOR) availability and liver activity in opioid use disorder (OUD) patients treated with methadone (MET) or buprenorphine (BUP). 10 OUD patients, 5 treated with MET and 5 with BUP, as well as 13 healthy controls (HCs) underwent total-body PET [¹¹C]carfentanil (CFN) imaging. MOR availability was quantified using distribution volume ratio (DVR) in key MOR-rich brain regions, and hepatic distribution volume (Vt) was used as an index of systemic tracer pharmacokinetics. Serum drug levels were measured in the OUD patients. Brain MOR availability was significantly lower in the OUD groups relative to HCs (p < 0.001), more so in BUP-treated (mean MOR difference = 39.9 ± 15.9%, Cohen's d = 3.35) than MET-treated (mean MOR difference = 14.2 ± 9.9%, d = 1.90) patients. Central MOR availability was inversely related to serum drug levels, linearly in MET treated (R2 = 0.83) and logarithmically in BUP-treated (R2 = 0.96), consistent with distinct receptor occupancy dynamics. Hepatic Vt differed across groups (p < 0.003) with levels in both OUD groups lower than in HCs (p < 0.05). In MET-treated patients, hepatic Vt was strongly associated with brain MOR availability (R² = 0.68), and inversely associated with serum drug levels (R² = 0.63). This relationship was less pronounced in BUP-treated patients (R² = 0.30), and absent in HCs. Drug-specific, brain-liver pharmacokinetic profiles were observed in OUD patients treated with MET versus BUP. While MET patients demonstrated coupling between hepatic tracer kinetics and brain receptor occupancy, BUP patients did not. These findings demonstrate that drug-specific brain-body pharmacokinetics may underscore observed clinical differences in opioid agonist effects in OUD.