Hugh Giovinazzo1,2, Parag Kumar1,3, Arif Sheikh4, Kristina M Brooks3, Marija Ivanovic4, Mark Walsh1, Whitney P Caron1, Richard J Kowalsky4, Gina Song1, Ann Whitlow4, Daniel L Clarke-Pearson4,5,6, Wendy R Brewster4,5,6, Linda Van Le4,5,6, Beth A Zamboni7, Victoria Bae-Jump4,5,6, Paola A Gehrig4,5,6, William C Zamboni8,9,10,11,12. 1. 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. 2. Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD, 21205, USA. 3. Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Clinical Center Pharmacy Department, 10 Center Drive Bldg. 10, 1C-240G, Bethesda, MD, 20892, USA. 4. UNC School of Medicine, 321 S. Columbia St., Chapel Hill, NC, 27599, USA. 5. 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. 6. UNC Lineberger Comprehensive Cancer Center, 101 Manning Drive, Chapel Hill, NC, 27514, USA. 7. Department of Mathematics, Carlow University, Pittsburgh, PA, USA. 8. 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. 9. UNC Lineberger Comprehensive Cancer Center, 101 Manning Drive, Chapel Hill, NC, 27514, USA. zamboni@email.unc.edu. 10. UNC Institute for Pharmacogenomics and Individualized Therapy, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu. 11. Carolina Center of Cancer Nanotechnology Excellence, 1079 Genetic Medicine Building, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu. 12. North Carolina Biomedical Innovation Network, 013 Genetic Medicine Building CB#7361, Chapel Hill, NC, 27599, USA. zamboni@email.unc.edu.
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.
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.
Authors: Juliana O Silva; Renata S Fernandes; Sávia C A Lopes; Valbert N Cardoso; Elaine A Leite; Geovanni D Cassali; Maria Cristina Marzola; Domenico Rubello; Monica C Oliveira; Andre Luis Branco de Barros Journal: Mol Imaging Biol Date: 2016-12 Impact factor: 3.488
Authors: Brittney R Starling; Parag Kumar; Andrew T Lucas; David Barrow; Laura Farnan; Laura Hendrix; Hugh Giovinazzo; Gina Song; Paola Gehrig; Jeannette T Bensen; William C Zamboni Journal: Cancer Chemother Pharmacol Date: 2018-10-16 Impact factor: 3.333
Authors: Alexandros Marios Sofias; Yohana C Toner; Anu E Meerwaldt; Mandy M T van Leent; Georgios Soultanidis; Mattijs Elschot; Haruki Gonai; Kristin Grendstad; Åsmund Flobak; Ulrike Neckmann; Camilla Wolowczyk; Elizabeth L Fisher; Thomas Reiner; Catharina de Lange Davies; Geir Bjørkøy; Abraham J P Teunissen; Jordi Ochando; Carlos Pérez-Medina; Willem J M Mulder; Sjoerd Hak Journal: ACS Nano Date: 2020-05-20 Impact factor: 15.881