Athymic rats in preclinical immunodiagnostic studies.
The usefulness of nude rat xenograft systems in immunolocalization studies was investigated using the monoclonal antibody 9.2.27 which binds to melanomas and osteosarcomas. Three human tumors, two melanomas (LOX and FEMX-I) and one osteosarcoma (OHSX), were used. They were established as s.c. xenografts in congenitally athymic (rnu/rnu) nude rats. These serially transplantable tumors showed the same morphology, take rate and growth properties in nude rats as in nude mice. Radiolabeled 9.2.27 F(ab')2 fragments injected i.v. into nude rats were concentrated in s.c. LOX and OHSX xenografts, reaching tumor to blood ratios of up to 30 after 3-4 days. However, the injected antibody failed to concentrate in FEMX-I xenografts, in contrast to previous findings in mice. This discrepancy could be attributed neither to significant differences in in vivo distribution of the labeled antibody nor to the presence of blocking factors in the serum of nude rats. In immunoscintigraphic studies clear images of s.c. LOX tumors were obtained, whereas lung colonies were less well visualized. Biodistribution studies showed a low tumor to blood ratio of about 4 in the latter animals, suggesting a tumor site-dependent variation in homing of labeled antibodies. Radiography was found to be superior to immunoscintigraphy in detecting the lung tumors. The present findings demonstrate that results of immunolocalization studies in nude mice cannot readily be extrapolated to other species. For the purpose of preclinical evaluation of new methods in cancer diagnosis and treatment, tumor xenografts in nude rats may represent a valuable complement to nude mouse models.
Storeng
R T
RT
Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo.
Kjønniksen
I
I
Pihl
A
A
Haug
E
E
Fodstad
O
O
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics; D007159:Immunologic Tests; D007457:Iodine Radioisotopes; D008545:Melanoma / Q000000981:diagnostic imaging / Q000473:pathology*; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000473:pathology*; D011859:Radiography; D011877:Radionuclide Imaging; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes