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Peer-reviewedCC BY 4.0European Journal of Nuclear Medicine and Molecular Imaging

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

  • Elizabeth J. Li1
  • Corinde E. Wiers2
  • Chia-Ju Hsieh1
  • Hsiaoju Lee1
  • Alexander Schmitz1
  • Anthony J. Young1
  • Timothy Pond2
  • Joseph Chang1
  • Erin K. Schubert1
  • Robert H. Mach1
  • Henry R. Kranzler2,3
  • Jacob G. Dubroff1
  1. 1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
  2. 2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
  3. 3Mental Illness Research, Education and Clinical Center, Crescenz VAMC, Philadelphia, PA 191 04 USA
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Abstract

Purpose: 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).

Methods: 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.

Results: 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.

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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08144-2.

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Cite

BibTeXRIS
BibTeX
@article{li2026totalbody,
  title = {{Total-body [11C]carfentanil PET: Liver-brain axis in methadone vs. buprenorphine treatment}},
  author = {Elizabeth J. Li and Corinde E. Wiers and Chia-Ju Hsieh and Hsiaoju Lee and Alexander Schmitz and Anthony J. Young and Timothy Pond and Joseph Chang and Erin K. Schubert and Robert H. Mach and Henry R. Kranzler and Jacob G. Dubroff},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = aug,
  doi = {10.1007/s00259-026-08144-2},
  url = {https://doi.org/10.1007/s00259-026-08144-2},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Total-body [11C]carfentanil PET: Liver-brain axis in methadone vs. buprenorphine treatment
AU  - Elizabeth J. Li
AU  - Corinde E. Wiers
AU  - Chia-Ju Hsieh
AU  - Hsiaoju Lee
AU  - Alexander Schmitz
AU  - Anthony J. Young
AU  - Timothy Pond
AU  - Joseph Chang
AU  - Erin K. Schubert
AU  - Robert H. Mach
AU  - Henry R. Kranzler
AU  - Jacob G. Dubroff
PY  - 2026
DA  - 2026/08/22
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08144-2
UR  - https://doi.org/10.1007/s00259-026-08144-2
AB  - Purpose: 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).  Methods: 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.  Results: 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.  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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08144-2.
SN  - 1619-7070
SN  - 1619-7089
ER  -