Two-step targeting and dosimetry for small cell lung cancer xenograft with anti-NCAM/antihistamine bispecific antibody and radioiodinated bivalent hapten.
The "affinity enhancement system," a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody.


METHODS
Antineural cell adhesion molecule/antihistamine bispecific antibody NK1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NCI-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 125I-labeled bivalent histamine hapten. 125I-labeled intact NK1NBL1 was injected into other groups of mice. Biodistributions were examined as a function of time.


RESULTS
In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7, respectively, at 5 h, whereas 125I-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrated clear tumor-to-normal tissue contrast. Dosimetry showed that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1.


CONCLUSIONS
This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer.
Hosono
M
M
Department of Radiology, Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
Hosono
M N
MN
Kraeber-Bodéré
F
F
Devys
A
A
Thédrez
P
P
Faivre-Chauvet
A
A
Gautherot
E
E
Barbet
J
J
Chatal
J F
JF
D000818:Animals; D018033:Antibodies, Bispecific; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D005260:Female; D006241:Haptens; D006632:Histamine / Q000276:immunology*; D006801:Humans; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D019006:Neural Cell Adhesion Molecules / Q000276:immunology*; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D018033:Antibodies, Bispecific; D006241:Haptens; D007457:Iodine Radioisotopes; D019006:Neural Cell Adhesion Molecules; D006632:Histamine