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

Ande Bao, Beth Goins, Robert Klipper, George Negrete, William T. Phillips

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)419-425
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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