Effect of hyperthermia on tumor uptake of radiolabeled anti-neural cell adhesion molecule antibody in small-cell lung cancer xenografts.
This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells.


METHODS
Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bearing NCI-H69 were either sham-treated or treated by a single hyperthermia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr.


RESULTS
NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fold increase in the tumor uptake of 125I- and 111In-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake.


CONCLUSIONS
Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.
Hosono
M N
MN
Department of Radiology, Osaka City University School of Medicine, Japan.
Hosono
M
M
Endo
K
K
Ueda
R
R
Onoyama
Y
Y
D000818:Animals; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D013997:Time Factors; D014018:Tissue Distribution
D015816:Cell Adhesion Molecules, Neuronal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes