BIODISTRIBUTION OF I-125 MAB 425 IN A HUMAN GLIOMA XENOGRAFT MODEL - EFFECT OF CHLOROQUINE

Chloroquine has been shown to increase the cellular retention and nucl ear incorporation of I-125-labeled monoclonal antibody (MAb) 425, a mu rine anti-epidermal growth factor receptor monoclonal antibody, in hum an high-grade glioma cells in vitro. The objective of this study was t o examine the effect of chloroquine on the biodistribution of (125)MAb 425 in an intracerebral xenogeneic transplant of glioma cells, Nude r ats were stereotaxically implanted in the right hemisphere with A1207 human high-grade glioma cells. After 14 days, animals were injected i. v. with chloroquine (40 mg/kg) followed 2 h later by an I-125-MAb 425 (9 MBq) infusion. Tissue distributions were peformed up to 168 h post I-125-MAb 425 injection, From 24 to 168 h, tumor-to-contralateral left brain ratios increased from 9 to 15 for I-125-MAb 425 alone, and 7 to 13 for the I-125-MAb 425/chloroquine combination, respectively. A sin gle administration of chloroquine did not result in any significant di fference in radiolabeled MAb accumulation in either the tumor site or other tissues, We conclude that chloroquine did not increase the amoun t of I-125-MAb 425 into the tumor; however, it is safe to administer i .v. at the 40 mg/kg dose. Under these experimental conditions, the inc reased radioactive accumulation observed for in vitro data did not tra nslate into similar in vivo results.