Tumour localization and pharmacokinetics of iodine-125 human monoclonal IgM antibody (COU-1) and its monomeric and half-monomeric fragments analysed in nude mice grafted with human tumour.
Human monoclonal IgM antibodies reactive with cancer-associated antigens may not have the optimal imaging capability due to their large size. Fragmentation of human IgM is less than straight-forward due to the loss of immunoreactivity. From the human monoclonal IgM antibody COU-1 we have prepared monomeric and half-monomeric fragments, which retain the ability to bind to colon cancer cells in vitro. The pharmacokinetics and tumour localization were evaluated in nude mice bearing human colon adenocarcinoma and human melanoma grafts. Faster clearance from the circulation was seen for the smaller half-monomeric fragment with a half-life (rapid phase/slow phase) of 2 h/16 h compared with the intact antibody, 4 h/25 h, and the monomeric fragment, 3 h/27 h. Intact COU-1 as well as the fragments accumulated in the colon tumour graft. Higher amounts of radioactivity were found in the colon tumour as compared to normal organs for intact COU-1 at days 4 and 6, for the monomeric fragment at day 4, and for the half-monomeric fragment at day 2 after injection. This investigation demonstrates the favourable biodistribution of the half monomeric COU-1 fragment. The fast clearance of this fragment resulted in a tumour-to-muscle ratio as high as 22 on day 2 after injection. Also, only this fragment gave a positive tumour-to-blood ratio. Normal IgM and its fragments were used as controls. Radioimmunoscintigraphy demonstrated the colon tumour discriminatory properties of each of the three iodine-labelled antibody preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Ditzel
H
H
Department of Medical Microbiology, University of Odense Medical Centre, Denmark.
Rasmussen
J W
JW
Erb
K
K
Jensenius
J C
JC
D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes; D008545:Melanoma / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D014018:Tissue Distribution
D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes