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Monoclonal antibody radiopharmaceuticals: Cationization, pegylation, radiometal chelation, pharmacokinetics, and tumor imaging

Title
Monoclonal antibody radiopharmaceuticals: Cationization, pegylation, radiometal chelation, pharmacokinetics, and tumor imaging
Authors
Lee H.J.Pardridge W.M.
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2003
Journal Title
Bioconjugate Chemistry
ISSN
1043-1802JCR Link
Citation
vol. 14, no. 3, pp. 546 - 553
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The 528 murine monoclonal antibody (MAb) to the human epidermal growth factor receptor (EGFR) was sequentially cationized with hexamethylenediamine and conjugated with diethylenetriaminepentaacetic acid (DTPA) as a potential antibody radiopharmaceutical for imaging EGFR-expressing cancer. The cationized 528 MAb was characterized with isoelectric focusing and electrophoresis, and an immunoradiometric assay, which showed the affinity of the 528 MAb for the human EGFR was retained following cationization. The native or cationized 528 MAb, labeled with 111In, was injected intravenously in scid mice bearing human U87 flank tumors, which express the EGFR, and tumor imaging was performed with both external detection in live animals and with whole body autoradiography. However, the tumor signal was not increased with the cationized MAb, relative to the native MAb, and this was due to a serum inhibition phenomenon that was confirmed by a pharmacokinetics analysis in control mice. In an attempt to block the serum inhibition, the cationized 528 MAb was pegylated with 2000 Da poly(ethylene glycol), and the cationized/pegylated MAb was conjugated with DTPA and labeled with 111In. However, a pharmacokinetics analysis showed the pegylation did not reverse the serum inhibition of the cationic charge on the MAb. These studies describe methods for reformulating monoclonal antibodies to develop improved radiopharmaceuticals, but show that radiolabeling a cationized MAb with DTPA produces a serum neutralization of the initial cationization modification.
DOI
10.1021/bc0256648
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약학대학 > 약학과 > Journal papers
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