Repeat injection studies of technetium-99m-labeled PEG-liposomes in the same animal

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Abstract

This study was designed to determine if repeat injections of polyethylene glycol (PEG) coated liposomes in the same animal lead to a change in biodistribution due to a biological response. To evaluate the long- term storage of PEG-liposomes for imaging applications and to remove any concerns of batch variability, one large batch of PEG-liposomes containing glutathione and sucrose was prepared and used for the entire study. On each day that an imaging study was performed, an aliquot of PEG-liposomes were labeled with technetium-99m (99mTc) using hexamethylpropyleneamine oxime. Rabbits (n = 4) were injected with 99mTc-PEG-liposomes (2 ml; 13 mg phospholipid/kg body wt; 2 mCi 99mTc-activity) at 8 days after manufacture and imaged under a gamma camera. Heart-to-lung ratios, heart-to-liver ratios and organ activities were determined by region of interest analysis. Blood samples were collected to generate blood clearance curves. Six weeks later the same rabbits were given a second dose of 99mTc-PEG-liposomes at 50 days after manufacture and imaged as before. A set of new rabbits (n = 3) were also imaged at six weeks using 99mTC-PEG-liposomes in order to differentiate any differences in organ distribution due to storage vs. reinjection. Images acquired for each set of rabbits at 30 minutes demonstrated little change in organ distribution following reinjection. Heart-to-lung ratios decreased from 2.25 ± 0.06 at baseline to 2.05 0.05 on reinjection and 2.10 ± 0.01 upon storage. Heart-to-liver ratios were 1.46 ± 0.06 on reinjection, significantly lower than the ratio of 1.72 ± 0.10 at baseline or 1.68 ± 0.09 upon storage. Circulation half-life of 29 hours did not change within the three groups. Although a slight change in organ biodistribution occurred with storage and reinjection, these effects were minimal and are not likely to affect drug targeting or diagnostic imaging on repeat injection.

Original languageEnglish (US)
Pages (from-to)265-281
Number of pages17
JournalJournal of Liposome Research
Volume8
Issue number2
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Pharmaceutical Science

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