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Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer.

Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill-Eshelman School of Pharmacy, 120 Mason Farm Road, Suite 1013, CB 7361, Chapel Hill, NC, 27599-7361, USA. Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, 21205, USA. Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Clinical Center Pharmacy Department, 10 Center Drive Bldg. 10, 1C-240G, Bethesda, MD, 20892, USA. UNC School of Medicine, 321 S. Columbia St., Chapel Hill, NC, 27599, USA. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC Lineberger Comprehensive Cancer Center, 103B Physicians' Office Building CB# 7572, Chapel Hill, NC, 27599, USA. UNC Lineberger Comprehensive Cancer Center, 101 Manning Drive, Chapel Hill, NC, 27514, USA. Department of Mathematics, Carlow University, Pittsburgh, PA, USA. Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill-Eshelman School of Pharmacy, 120 Mason Farm Road, Suite 1013, CB 7361, Chapel Hill, NC, 27599-7361, USA. zamboni@email.unc.edu. UNC Lineberger Comprehensive Cancer Center, 101 Manning Drive, Chapel Hill, NC, 27514, USA. zamboni@email.unc.edu. UNC Institute for Pharmacogenomics and Individualized Therapy, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu. Carolina Center of Cancer Nanotechnology Excellence, 1079 Genetic Medicine Building, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu. North Carolina Biomedical Innovation Network, 013 Genetic Medicine Building CB#7361, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu.

Cancer chemotherapy and pharmacology. 2016;(3):565-73
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Abstract

PURPOSE 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. METHODS TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30-40 mg/m(2) IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling. RESULTS 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. CONCLUSIONS 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.

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Publication Type : Clinical Trial

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