SIR 2024
Interventional Oncology
Andrew Mikhail, PhD
Staff Scientist
National Institutes of Health
Financial relationships: Full list of relationships is listed on the CME information page.
Ivane Bakhutashvili, MD PhD
Research staff
National Institutes of Health
Disclosure information not submitted.
William Figg, PHARMD
Senior Investigator
National Institutes of Health, United Kingdom
Disclosure information not submitted.
Tim Greten, MD
Principle Investigator
National Institutes of Health
Disclosure information not submitted.
John Karanian, PhD
Staff Scientist
National Institutes of Health, Clinical Center
Disclosure information not submitted.
William Pritchard, MD, PhD
Medical Officer
National Institutes of Health Clinical Center
Disclosure information not submitted.
Bradford J. Wood, MD, FSIR
Director NIH Center for IO, Chief IR
NIH
Financial relationships: Full list of relationships is listed on the CME information page.
To evaluate plasma pharmacokinetics of a small molecule PD-L1 checkpoint inhibitor following embolization of woodchuck hepatocellular carcinoma (HCC) with radiopaque drug-eluting beads (DEB).
Materials and Methods:
Woodchucks with HCC (N=8) underwent transarterial embolization with radiopaque DEB (40-90 μm, LC Bead LUMI) loaded with a small molecule PD-L1 checkpoint inhibitor, BMS-202. Peripheral blood samples were collected during selective hepatic embolization and for 4 hours following arterial stasis. Following euthanasia, the liver was resected and micro-CT was performed to visualize DEB distribution. BMS-202 was measured in serum and tissue samples using LC/MS. All procedures were approved by the Animal Care and Use Committee.
Results:
The mean bead volume and dose administered were 0.4 mL (0.09-0.65 mL) and 0.25 mg/kg (0.06-0.41 mg/kg), respectively. Quantifiable drug concentrations in serum were detected in 7 woodchucks, and 2 were excluded from PK analysis due to termination before 4h. Maximum serum concentration (Cmax) occurred 4 hours post embolization, the terminal sample timepoint before euthanasia. Dose-normalized serum Cmax and Area Under the Curve (AUC) were 10.13 ± 4.13 ng/mL/mg and 30.46 ± 14.60 hr*ng/mL/mg, respectively. Elevated concentrations of BMS-202 were found in target tumors.
Conclusion:
Acute plasma pharmacokinetics of a small molecule PD-L1 checkpoint inhibitor after embolization and release from DEB suggest controlled drug elution in vivo, similar to doxorubicin-loaded DEB, without rapid elevation in systemic drug concentration. Although speculative, locoregional delivery of immunomodulators during immuno-embolization with Immuno-Beads (immuno-DEB) may minimize systemic drug toxicity. Subsequent in vivo assessments will include survival studies to assess safety and efficacy.