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 mo del. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NC AM) expressed by human small-cell lung cancer (SCLC) cells. Methods: A thymic mice inoculated with NCI-H69, an SCLC cell line, received an in travenous injection of I-125- and In-111-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bear ing NCI-H69 were either sham-treated or treated by a single hypertherm ia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing le g in a water bath using pentobarbital anesthesia. Immediately after he ating, the mice were given an intravenous injection of radiolabeled NE 150, and the biodistribution was examined at 24 and 48 hr. Results: NE 150 localized well in the transplanted tumor when compared with a cont rol Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fo ld increase in the tumor uptake of I-125- and In-111-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 radi olabeled NE150 cleared faster from the circulation in the mice given h yperthermia. A histological study demonstrated the infiltration of neu trophils in the perivascular spaces, indicating an increase of tumor v ascular permeability, which might be one of the main reasons for the e nhancement of Mab uptake. Conclusion: Hyperthermia seems to be a poten tial method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.