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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Direct 99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Ande Bao, Beth Goins, Robert Klipper, George Negrete and William T. Phillips
Journal of Pharmacology and Experimental Therapeutics February 2004, 308 (2) 419-425; DOI: https://doi.org/10.1124/jpet.103.059535
Ande Bao
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Beth Goins
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Robert Klipper
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George Negrete
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William T. Phillips
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Abstract

Pharmacokinetic and organ distribution studies of liposomal drugs in humans are a challenge. A direct labeling method using 99mTc-N,N-bis(2-mercaptoethyl)-N′,N′-diethyl-ethylenediamine (BMEDA) complex to label the commercially available pegylated liposomal doxorubicin, Doxil, has been introduced. Biodistributions of 99mTc-Doxil in normal rats were performed to evaluate the feasibility of using it for monitoring the pharmacokinetics of liposomes encapsulating drugs. Labeling efficiency of 99mTc-Doxil was 70.6 ± 0.8% (n = 3). In vitro incubation of 99mTc-Doxil in 50% fetal bovine serum or 50% human serum at 37°C showed good labeling stability with 72.3 ± 3.6% or 78.6 ± 1.8% of activity associated with Doxil at 24 h, respectively (n = 3). There was a two-phase blood clearance with half-clearance times of 2.2 and 26.2 h after bolus intravenous injection in normal rats. Distribution of 99mTc-Doxil at 44 h after injection had 19.8 ± 1.3% of injected dose in blood, 14.1 ± 1.7% in liver, 2.6 ± 0.3% in spleen, 9.0 ± 0.8% in bone with marrow, 6.0 ± 0.5% in skin, and 15.3 ± 4.3% in bowel (n = 5). Unencapsulated 99mTc-BMEDA had a very rapid blood clearance with a half-clearance time of only 0.12 h (n = 4). By using this 99mTc labeling method, biodistribution and pharmacokinetics of ammonium gradient liposomes encapsulating drugs can be determined by noninvasive scintigraphic imaging. This labeling method may be extended to 186Re and 188Re labeling to combine chemotherapy and radionuclide therapy for tumor treatment.

Footnotes

  • We thank the San Antonio Area Foundation for financial support.

  • DOI: 10.1124/jpet.103.059535.

  • ABBREVIATIONS: BMEDA, N,N-bis(2-mercaptoethyl)-N′,N′-diethyl-ethylenediamine; GH, glucoheptonate; 99mTc, technetium-99m; 111In, indium-111; FBS, fetal bovine serum; PBS, phosphate-buffered saline.

    • Received September 3, 2003.
    • Accepted October 24, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 308 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 308, Issue 2
1 Feb 2004
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Direct 99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Ande Bao, Beth Goins, Robert Klipper, George Negrete and William T. Phillips
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 419-425; DOI: https://doi.org/10.1124/jpet.103.059535

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Direct 99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Ande Bao, Beth Goins, Robert Klipper, George Negrete and William T. Phillips
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 419-425; DOI: https://doi.org/10.1124/jpet.103.059535
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