Radiotherapy of CD45-expressing Daudi tumors in nude mice with yttrium-90-labeled, PEGylated anti-CD45 antibody

Daniel A Vallera, Andy R. Sicheneder, Elizabeth P. Taras, Martin W. Brechbiel, Jesse A. Vallera, Angela Panoskaltsis-Mortari, Linda J. Burns

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Studies were performed to determine the suitability of using the polyethylene glycol (PEG)-labeled AHN-12 anti-CD45 monoclonal antibody to deliver the high-energy β-particle-emitting isotope 90Y to a CD45+ B-cell Daudi lymphoma grown as flank tumors in athymic nude mice. The PEGylated radiolabeled antibody displayed a significantly better antitumor effect in the mouse tumor flank model (p < 0.03) and significantly better blood pharmacokinetics in normal rats (p < 0.05) than the non-PEGylated radiolabeled antibody. Studies of two different sizes of PEG showed that rats given 43 kDa of PEGylated AHN-12, but not 5 kDa of PEGylated AHN-12, had significantly higher radiolabeled antibody blood levels and, therefore, improved pharmacokinetics, as compared to rodents given non-PEGylated radiolabeled AHN-12 (p < 0.05). Surviving mice revealed no signs of kidney, liver, or gastrointestinal damage by histology study. Notably, in vitro studies indicated that PEGylation did not have a major effect on labeling efficiency and the binding of labeled antibody. These findings indicate that PEGylation of radiolabeled anti-CD45 antibody may be a useful and desirable means of extending blood half-life and enhancing efficacy. Also, the final outcome may be impacted by the size of the PEG molecule used for the modification of the blood half-life.

Original languageEnglish (US)
Pages (from-to)488-500
Number of pages13
JournalCancer Biotherapy and Radiopharmaceuticals
Volume22
Issue number4
DOIs
StatePublished - Aug 2007

Keywords

  • Anti-CD45
  • Bone marrow transplantation
  • Leukemia
  • Lymphoma
  • Nude mice
  • PEG
  • PEGylated
  • Radioimmunoconjugate
  • Radiopharmaceutical
  • Tumor
  • Yttrium-90

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