Different biodistribution of 99mTc-labelled chimeric mouse-human monoclonal antibody between athymic mice model and human.
Biodistribution of chimeric mouse/human monoclonal antibody against non-specific cross-reacting antigen (chNCA Ab) was studied in athymic mice and patients with metastatic bone disease. 99mTc-chNCA Ab showed a high labelling efficiency, stability and also a high binding ratio to human granulocytes. Since NCA showed cross-reactivity with carcinoembryonic antigen (CEA), animal experiments showed that 99mTc-chNCA Ab was accumulated in the xenografted tumour which expressed CEA, suggesting the preserved immunoreactivity of labelled materials. In the clinical study, injected 99mTc-chNCA Ab formed a high molecular weight complex immediately after intravenous administration and was trapped mainly in liver. The first-phase plasma half-life was 6.4 +/- 1.1 min. None of the patients showed adverse reaction or human antimurine or anti-chimeric antibody in their serum. 99mTc-chNCA Ab demonstrated remarkably different biodistribution between patients and the animal model and showed different pharmacokinetics from other murine and chimeric Abs reported previously. For safety HPLC analysis should be performed before clinical radioimmunodetection or radioimmunotherapy by incubating radiolabelled MAb with human serum under strict conditions.
Oriuchi
N
N
Department of Nuclear Medicine, Gunma University School of Medicine, Maebashi, Japan.
Watanabe
N
N
Sugiyama
S
S
Higuchi
T
T
Imai
K
K
Yamanaka
H
H
Hashimoto
M
M
Kanda
H
H
Endo
K
K
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000951:Antigens, Neoplasm / Q000276:immunology; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000556:secondary; D015815:Cell Adhesion Molecules; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D016719:Radioimmunodetection; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D013670:Sodium Pertechnetate Tc 99m