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01.03.2016 | Original Article

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

verfasst von: 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. Zamboni

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2016

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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/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.

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Titel: Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer
verfasst von: 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. Zamboni
Publikationsdatum: 01.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2945-y

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Springer Medizin

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

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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