Treatment of small-cell lung cancer xenografts with iodine-131-anti-neural cell adhesion molecule monoclonal antibody and evaluation of absorbed dose in tissue.
Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC.


METHODS
To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with 131I and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of 131I-NE150.


RESULTS
Tumors (initial volume 563.4 +/- 223.5 mm3) treated with 11.1 MBq (300 microCi) of 131I-NE150 diminished and became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively.


CONCLUSIONS
Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.
Hosono
M
M
Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Japan.
Endo
K
K
Hosono
M N
MN
Kobayashi
H
H
Shirato
M
M
Sakahara
H
H
Ueda
R
R
Konishi
J
J
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000532:radiotherapy*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal