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 language | English (US) |
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Pages (from-to) | 488-500 |
Number of pages | 13 |
Journal | Cancer Biotherapy and Radiopharmaceuticals |
Volume | 22 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2007 |
Keywords
- Anti-CD45
- Bone marrow transplantation
- Leukemia
- Lymphoma
- Nude mice
- PEG
- PEGylated
- Radioimmunoconjugate
- Radiopharmaceutical
- Tumor
- Yttrium-90