Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 3/2016

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

Authors: 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

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2016

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Centocor Ortho Biotech Products (2011) Doxil® (doxorubicin HCl liposome injection) package insert. Raritan, NJ
2.
Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D (1999) Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 51(4):691–743PubMed
3.
Papahadjopoulos D, Allen TM, Gabizon A, Mayhew E, Matthay K, Huang SK, Lee KD, Woodle MC, Lasic DD, Redemann C (1991) Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 88(24):11460–11464PubMedCentralCrossRefPubMed
4.
5.
Allen TM, Stuart DD (1999) Liposomal pharmacokinetics: classical, sterically stabilized, cationic liposomes and immunoliposomes. In: Janoff AS (ed) Liposomes: rational design. Marcel Dekker, New York
6.
Allen TM, Hansen C (1991) Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta 1068(2):133–141CrossRefPubMed
7.
Working PK, Newman MS, Huang SK, Mayhew E, Vaage J, Lasic DD (1994) Pharmacokinetics, biodistribution and therapeutic efficacy of doxorubicin encapsulated in Stealth® liposomes (Doxil®). J Liposome Res 4(1):667–687CrossRef
8.
Kalvass JC, Graff CL, Pollack GM (2004) Use of loperamide as a phenotypic probe of mdr1a status in CF-1 mice. Pharm Res 21(10):1867–1870CrossRefPubMed
9.
Pharmalucence (2012) Package insert for kit for the preparation of technetium Tc 99m sulfur colloid injection diagnostic for intravenous and oral use. Billerica, MA
10.
Shih WJ, Domstad PA, DeLand FH, Purcell M (1985) Simultaneous demonstration of pleural effusion and ascites by technetium-99 m sulfur colloid liver-spleen scintigraphy. Clin Nucl Med 10(9):637–638CrossRefPubMed
11.
Shih WJ, Domstad PA, Friedman B, DeLand FH (1986) Intrathoracic abnormalities demonstrated by technetium-99 m sulfur colloid imaging. Clin Nucl Med 11(11):792–796CrossRefPubMed
12.
Kowalsky RJ, Falen SW (2004) Radiopharmaceuticals in nuclear pharmacy and nuclear medicine. In: 3rd edn. American Pharmacists Association, Washington, p 199
13.
Seidner DL, Mascioli EA, Istfan NW, Porter KA, Selleck K, Blackburn GL, Bistrian BR (1989) Effects of long-chain triglyceride emulsions on reticuloendothelial system function in humans. J Parenter Enteral Nutr 13(6):614–619CrossRef
14.
Koukourakis MI, Koukouraki S, Giatromanolaki A, Archimandritis SC, Skarlatos J, Beroukas K, Bizakis JG, Retalis G, Karkavitsas N, Helidonis ES (1999) Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer. J Clin Oncol 17(11):3512–3521PubMed
15.
Gmeiner Stopar T, Fettich J, Zver S, Mlinaric-Rascan I, Hojker S, Socan A, Peitl PK, Mather S (2008) 99 mTc-labelled rituximab, a new non-Hodgkin’s lymphoma imaging agent: first clinical experience. Nucl Med Commun 29(12):1059–1065. doi:10.​1097/​MNM.​0b013e3283134d6e​ CrossRefPubMed
16.
Pfeifer ND, Goss SL, Swift B, Ghibellini G, Ivanovic M, Heizer WD, Gangarosa LM, Brouwer KL (2013) Effect of ritonavir on (99 m) technetium–mebrofenin disposition in humans: a semi-PBPK modeling and in vitro approach to predict transporter-mediated DDIs. CPT Pharmacomet Syst Pharmacol 2:20. doi:10.​1038/​psp.​2012.​21 CrossRef
17.
Newman MS, Colbern GT, Working PK, Engbers C, Amantea MA (1999) Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in tumor-bearing mice. Cancer Chemother Pharmacol 43(1):1–7. doi:10.​1007/​s002800050855 CrossRefPubMed
18.
Zamboni WC, Gervais AC, Egorin MJ, Schellens JH, Zuhowski EG, Pluim D, Joseph E, Hamburger DR, Working PK, Colbern G, Tonda ME, Potter DM, Eiseman JL (2004) Systemic and tumor disposition of platinum after administration of cisplatin or STEALTH liposomal-cisplatin formulations (SPI-077 and SPI-077 B103) in a preclinical tumor model of melanoma. Cancer Chemother Pharmacol 53(4):329–336. doi:10.​1007/​s00280-003-0719-4 CrossRefPubMed
19.
20.
21.
Vail DM, Amantea MA, Colbern GT, Martin FJ, Hilger RA, Working PK (2004) Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies. Semin Oncol 31(6 Suppl 13):16–35CrossRefPubMed
22.
Krown SE, Northfelt DW, Osoba D, Stewart JS (2004) Use of liposomal anthracyclines in Kaposi’s sarcoma. Semin Oncol 31(6 Suppl 13):36–52CrossRefPubMed
23.
24.
Markman M, Gordon AN, McGuire WP, Muggia FM (2004) Liposomal anthracycline treatment for ovarian cancer. Semin Oncol 31(6 Suppl 13):91–105CrossRefPubMed
25.
Martschick A, Sehouli J, Patzelt A, Richter H, Jacobi U, Oskay-Ozcelik G, Sterry W, Lademann J (2009) The pathogenetic mechanism of anthracycline-induced palmar-plantar erythrodysesthesia. Anticancer Res 29(6):2307–2313PubMed
26.
27.
28.
Caron WP, Song G, Kumar P, Rawal S, Zamboni WC (2012) Interpatient pharmacokinetic and pharmacodynamic variability of carrier-mediated anticancer agents. CPT Pharmacomet Syst Pharmacol 91(5):802–812. doi:10.​1038/​clpt.​2012.​12
29.
Zamboni WC, Maruca LJ, Strychor S, Zamboni BA, Ramalingam S, Edwards RP, Kim JK, Bang YJ, Lee HY, Friedland DM (2011) Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors. J Liposome Res 21(2):158–165CrossRefPubMed
30.
Zamboni WC, Eiseman JL, Strychor S, Rice PM, Joseph E, Zamboni BA, Donnelly MK, Shurer J, Parise RA, Tonda ME (2011) Tumor disposition of pegylated liposomal CKD-602 and the reticuloendothelial system in preclinical tumor models. J Liposome Res 21(1):70–80CrossRefPubMed
31.
La-Beck NM, Zamboni BA, Gabizon A, Schmeeda H, Amantea M, Gehrig PA, Zamboni WC (2012) Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol 69(1):43–50. doi:10.​1007/​s00280-011-1664-2 CrossRefPubMed
32.
Coleman RE, Blinder RA, Jaszczak RJ (1986) Single photon emission computed tomography (SPECT). Part II: clinical applications. Invest Radiol 21(1):1–11CrossRefPubMed
33.
Gabizon A, Isacson R, Rosengarten O, Tzemach D, Shmeeda H, Sapir R (2008) An open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin. Cancer Chemother Pharmacol 61(4):695–702. doi:10.​1007/​s00280-007-0525-5 CrossRefPubMed
34.
35.
Zamboni WC, Strychor S, Maruca L, Ramalingam S, Zamboni BA, Wu H, Friedland DM, Edwards RP, Stoller RG, Belani CP (2009) Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. CPT Pharmacomet Syst Pharmacol 86(5):519–526
36.
Nielsen H (1984) Effect of cis-platinum on human blood monocyte function in vitro. Cancer Immunol Immunother (CII) 18(3):223–225
37.
38.
Richardson DS, Johnson SA (1997) Anthracyclines in haematology: preclinical studies, toxicity and delivery systems. Blood Rev 11(4):201–223CrossRefPubMed
Metadata
Title
Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer
Authors
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
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2945-y

Other articles of this Issue 3/2016

Cancer Chemotherapy and Pharmacology 3/2016 Go to the issue

Original Article

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer

Review Article

Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs

Original Article

UCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy

Original Article

Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer

Original Article

Histone deacetylase 2 regulates doxorubicin (Dox) sensitivity of colorectal cancer cells by targeting ABCB1 transcription

Original Article

A pharmacodynamically guided dose selection of PF-00337210 in a phase I study in patients with advanced solid tumors
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits