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Cancer Chemotherapy and Pharmacology

, Volume 77, Issue 3, pp 565–573 | Cite as

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

  • Hugh Giovinazzo
  • Parag Kumar
  • Arif Sheikh
  • Kristina M. Brooks
  • Marija Ivanovic
  • Mark Walsh
  • Whitney P. Caron
  • Richard J. Kowalsky
  • Gina Song
  • Ann Whitlow
  • Daniel L. Clarke-Pearson
  • Wendy R. Brewster
  • Linda Van Le
  • Beth A. Zamboni
  • Victoria Bae-Jump
  • Paola A. Gehrig
  • William C. ZamboniEmail author
Original Article

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/m2 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.

Keywords

Pharmacokinetics Pharmacodynamics Liposomes TSC PEGylated liposomal doxorubicin Phenotypic probe Ovarian cancer 

Notes

Acknowledgments

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

280_2015_2945_MOESM1_ESM.pdf (253 kb)
Supplementary material 1 (PDF 253 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2016

Authors and Affiliations

  • Hugh Giovinazzo
    • 1
    • 2
  • Parag Kumar
    • 1
    • 3
  • Arif Sheikh
    • 4
  • Kristina M. Brooks
    • 3
  • Marija Ivanovic
    • 4
  • Mark Walsh
    • 1
  • Whitney P. Caron
    • 1
  • Richard J. Kowalsky
    • 4
  • Gina Song
    • 1
  • Ann Whitlow
    • 4
  • Daniel L. Clarke-Pearson
    • 4
    • 5
    • 6
  • Wendy R. Brewster
    • 4
    • 5
    • 6
  • Linda Van Le
    • 4
    • 5
    • 6
  • Beth A. Zamboni
    • 7
  • Victoria Bae-Jump
    • 4
    • 5
    • 6
  • Paola A. Gehrig
    • 4
    • 5
    • 6
  • William C. Zamboni
    • 1
    • 6
    • 8
    • 9
    • 10
    Email author
  1. 1.Division of Pharmacotherapy and Experimental TherapeuticsUniversity of North Carolina at Chapel Hill-Eshelman School of PharmacyChapel HillUSA
  2. 2.Department of Pharmacology and Molecular SciencesJohns Hopkins School of MedicineBaltimoreUSA
  3. 3.Clinical Pharmacokinetics Research LaboratoryNational Institutes of Health, Clinical Center Pharmacy DepartmentBethesdaUSA
  4. 4.UNC School of MedicineChapel HillUSA
  5. 5.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyUNC Lineberger Comprehensive Cancer CenterChapel HillUSA
  6. 6.UNC Lineberger Comprehensive Cancer CenterChapel HillUSA
  7. 7.Department of MathematicsCarlow UniversityPittsburghUSA
  8. 8.UNC Institute for Pharmacogenomics and Individualized TherapyChapel HillUSA
  9. 9.Carolina Center of Cancer Nanotechnology ExcellenceChapel HillUSA
  10. 10.North Carolina Biomedical Innovation NetworkChapel HillUSA

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