Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer
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Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer.
TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30–40 mg/m2 IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling.
There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R 2 = 0.61, p = 0.02), particularly in patients receiving PLD alone (R 2 = 0.81, p = 0.04). There was a positive relationship (ρ = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands.
TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development.
KeywordsPharmacokinetics Pharmacodynamics Liposomes TSC PEGylated liposomal doxorubicin Phenotypic probe Ovarian cancer
This study was funded by the Lineberger Comprehensive Cancer Center, UNC University Cancer Research Fund (UCRF) and the Carolina Center of Cancer Nanotechnology Excellence (C-CCNE) Pilot grant (NIH/NCI CA119343). The investigators would like to thank the faculty and staff of the UNC School of Medicine, Divisions of Gynecologic Oncology and Nuclear Medicine; UNC North Carolina Translational and Clinical Sciences Institute, Clinical and Translational Research Center; UNC Eshelman School of Pharmacy, Translational Oncology and Nanoparticle Drug Development Initiative Lab; the CCNE; and the patients, families, and friends who made this work possible.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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