Publications : 2016

Giovinazzo H, Kumar P, Sheikh A, Brooks KM, Ivanovic M, Walsh M, Caron WP, Kowalsky RJ, Song G, Whitlow A, Clarke-Pearson DL, Brewster WR, Van Le L, Zamboni BA, Bae-Jump V, Gehrig PA, Zamboni WC. 2016. Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer. Cancer Chemother Pharmcol 77(3):565–573.

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.