The effect of second antibody clearance on the distribution and dosimetry of radiolabelled anti-CEA antibody in a human colonic tumor xenograft model.
Radioimmunotherapy in humans is limited by toxicity to normal tissues, caused by circulating radio-antibody. Second antibody directed against the first (anti-tumor) antibody accelerates clearance of first antibody from normal tissues, and may thus improve the therapeutic ratio. The effect of second antibody both on anti-tumor antibody distribution and on tumor and normal tissue radiation doses, has been investigated in nude mice bearing colonic tumor xenografts. Second antibody, given either 6 or 24 hr after the first, rapidly cleared circulating activity and reduced the calculated radiation dose to all tissues except the spleen, where it rose by 11 and 43% respectively. The dose received by the blood fell by 87% and 71%, while that to the tumor was reduced by 81% and 58%, after 6 or 24 hr second antibody. Administration of second antibody therefore improved the tumor to blood ratios. Tumor identification by gamma camera was greatly facilitated by the use of second antibody, and required no background subtraction. Results obtained from this system demonstrate the utility of second antibody in protecting normal tissues from prolonged circulating radioactivity during radioimmunotherapy.
Pedley
R B
RB
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Dale
R
R
Boden
J A
JA
Begent
R H
RH
Keep
P A
PA
Green
A J
AJ
D002288:Adenocarcinoma, Mucinous / Q000276:immunology / Q000628:therapy*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013997:Time Factors; D014183:Transplantation, Heterologous
D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes