The pharmacokinetics of Zr-89 labeled liposomes over extended periods in a murine tumor model

Jai Seo, Lisa M. Mahakian, Sarah Tam, Shengping Qin, Elizabeth S. Ingham, Claude F. Meares, Katherine W. Ferrara

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

89Zr (t1/2=78.4h), a positron-emitting metal, has been exploited for PET studies of antibodies because of its relatively long decay time and facile labeling procedures. Here, we used 89Zr to evaluate the pharmacokinetics of long-circulating liposomes over 168h (1week). We first developed a liposomal-labeling method using p-isothiocyanatobenzyl-desferrioxamine (df-Bz-NCS) and df-PEG1k-DSPE. Df-Bz-NCS was conjugated to 1mol% amino- and amino-PEG2k-DSPE, where the 1mol% df-PEG1k-DSPE was incorporated when the liposomes were formulated. Incubation of 89Zr with df, df-PEG1k, and df-PEG2k liposomes for one hour resulted in greater than 68% decay-corrected yield. The loss of the 89Zr label from liposomes after incubation in 50% human serum for 48h ranged from ~1 to 3% across the three formulations. Tail vein administration of the three liposomal formulations in NDL tumor-bearing mice showed that the 89Zr label at the end of the PEG2k brush was retained in the tumor, liver, spleen and whole body for a longer time interval than 89Zr labels located under the PEG2k brush. The blood clearance rate of all three liposomal formulations was similar. Overall, the results indicate that the location of the 89Zr label altered the clearance rate of intracellularly-trapped radioactivity and that df-PEG1k-DSPE provides a stable chelation site for liposomal or lipid-based particle studies over extended periods of time.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalNuclear Medicine and Biology
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Liposomes
Pharmacokinetics
Neoplasms
Radioactivity
Tail
Veins
Spleen
Metals
Electrons
Lipids
1,2-distearoylphosphatidylethanolamine
Antibodies
Liver
Serum
4-isothiocyanatobenzyl-desferrioxamine

Keywords

  • Deferoxamine
  • Liposomes
  • Positron emission tomography
  • Zr-89

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

The pharmacokinetics of Zr-89 labeled liposomes over extended periods in a murine tumor model. / Seo, Jai; Mahakian, Lisa M.; Tam, Sarah; Qin, Shengping; Ingham, Elizabeth S.; Meares, Claude F.; Ferrara, Katherine W.

In: Nuclear Medicine and Biology, Vol. 42, No. 2, 01.02.2015, p. 155-163.

Research output: Contribution to journalArticle

Seo, Jai ; Mahakian, Lisa M. ; Tam, Sarah ; Qin, Shengping ; Ingham, Elizabeth S. ; Meares, Claude F. ; Ferrara, Katherine W. / The pharmacokinetics of Zr-89 labeled liposomes over extended periods in a murine tumor model. In: Nuclear Medicine and Biology. 2015 ; Vol. 42, No. 2. pp. 155-163.
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