Radio-iodinated and internally labelled (35S) IgM monoclonal antibodies in a syngenic rat model.
To simulate the human situation concerning human monoclonal antibodies (MAbs), we have introduced a new syngenic rat model with an implanted rat colon carcinoma. Rat IgM MAbs (10B12), labelled by the chloramine-T method with 125I or internally with 35S, were injected intravenously into the rats and the biodistribution was studied for 8 days. The radioactivity uptake in the tumours of the 35S label was higher than that of the 125I label and the retention of 35S in the tumours gave tumour/blood ratios 8 times higher than those of 125I at 48 and 96 h after injection. In this model we have shown that dehalogenation of iodinated IgM MAbs is a serious problem. We therefore suggest that internally labelled MAbs should be used and that further investigations should be carried out in a syngenic rat model, since this probably reflects the clinical situation better than the nude mouse model.
Wanying
Q
Q
Department of Nuclear Medicine, Beijing Hospital, China.
Brodin
T
T
Ceberg
C
C
Ingvar
C
C
Norrgren
K
K
Sjögren
H O
HO
Strand
S E
SE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002700:Chloramines; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D007075:Immunoglobulin M / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D009368:Neoplasm Transplantation; D051381:Rats; D011920:Rats, Inbred WF; D013462:Sulfur Radioisotopes; D013961:Thyroid Gland / Q000378:metabolism; D014018:Tissue Distribution; D014105:Tosyl Compounds
D000911:Antibodies, Monoclonal; D002700:Chloramines; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes; D013462:Sulfur Radioisotopes; D014105:Tosyl Compounds; C016300:chloramine-T