Biodistribution of 125I-MAb 425 in a human glioma xenograft model: effect of chloroquine.
Chloroquine has been shown to increase the cellular retention and nuclear incorporation of 125I-labeled monoclonal antibody (MAb) 425, a murine anti-epidermal growth factor receptor monoclonal antibody, in human high-grade glioma cells in vitro. The objective of this study was to examine the effect of chloroquine on the biodistribution of 125I-MAb 425 in an intracerebral xenogeneic transplant of glioma cells. Nude rats 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 125I-MAb 425 (9 MBq) infusion. Tissue distributions were performed up to 168 h post 125I-MAb 425 injection. From 24 to 168 h, tumor-to-contralateral left brain ratios increased from 9 to 15 for 125I-MAb 425 alone, and 7 to 13 for the 125I-MAb 425/chloroquine combination, respectively. A single administration of chloroquine did not result in any significant difference in radiolabeled MAb accumulation in either the tumor site or other tissues. We conclude that chloroquine did not increase the amount of 125I-MAb 425 into the tumor; however, it is safe to administer i.v. at the 40 mg/kg dose. Under these experimental conditions, the increased radioactive accumulation observed for in vitro data did not translate into similar in vivo results.
Emrich
J G
JG
Department of Radiation Oncology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
Hand
C M
CM
Dilling
T J
TJ
Class
R
R
Bender
H
H
Brady
L W
LW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000276:immunology*; D005910:Glioma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution / Q000187:drug effects; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002738:Chloroquine; D066246:ErbB Receptors