Radiotherapy of CD45-expressing Daudi tumors in nude mice with yttrium-90-labeled, PEGylated anti-CD45 antibody.
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 beta-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.
Vallera
Daniel A
DA
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. valle001@umn.edu
Sicheneder
Andy R
AR
Taras
Elizabeth P
EP
Brechbiel
Martin W
MW
Vallera
Jesse A
JA
Panoskaltsis-Mortari
Angela
A
Burns
Linda J
LJ
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D002852:Chromatography, Ion Exchange; D006801:Humans; D007167:Immunotherapy; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use*