Work

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

Year: 2026

Type: article

Abstract: Purpose 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). Methods 10 OUD patients, 5 treated with MET and 5 with BUP, as well as 13 healthy controls (HCs) underwent total-body PET [ 11 C]carfentanil (CFN) imaging. MOR availability was quantified via distribution volume ratio 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. Results MOR brain 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). Hepatic Vt was strongly associated with brain MOR availability (R 2 =0.68) across serum drug levels in MET patients (R 2 =0.63). This relationship was decoupled of this relationship in BUP patients (R 2 =0.30), and absent in HCs. Conclusions 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.

Source: European Journal of Nuclear Medicine and Molecular Imaging

DOI: 10.1007/s00259-026-08144-2