Biodistribution and dosimetric study in medullary thyroid cancer xenograft using bispecific antibody and iodine-125-labeled bivalent hapten.
The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and 125I-labeled DTPA-indium dimer hapten (125I-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer.


METHODS
Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, 125I-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of 125I-di-DTPA-In hapten or 125I-labeled F6 F(ab')2.


RESULTS
In mice injected with BsMAb F6-734 and 125I-di-DTPA-In hapten, tumor uptake was 9.1%+/-2.1%, 8.7%+/-3.5%, 8.0%+/-2.3%, 5.1%+/-0.9% and 3.5%+/-1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0+/-12.5, 32.3+/-10.9 and 10.4+/-2.7 at 24 hr. Iodine-125-F6 F(ab')2 fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8+/-0.6, 7.3+/-2.9 and 3.6+/-1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast.


CONCLUSIONS
This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.
Hosono
M
M
Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
Hosono
M N
MN
Kraeber-Bodéré
F
F
Devys
A
A
Thédrez
P
P
Fiche
M
M
Gautherot
E
E
Barbet
J
J
Chatal
J F
JF
D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology; D018276:Carcinoma, Medullary / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D018033:Antibodies, Bispecific; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes