In vivo SPECT/CT imaging of human ovarian carcinoma with monoclonal antibodies to EGFR and VEGFR-3 in mouse model

Objectives Endothelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor 3 (VEGFR-3) are implicated in tumor progression in several types of cancers and are targets in development of new therapies. Monoclonal antibodies, developed against these receptors, have shown to interfere the growth of the tumors by inhibiting the function of the receptors. During the development of ovarian carcinoma both receptors are expressed in tumors and are good targets for the corresponding monoclonal antibodies.

Methods We have studied the long term biodistribution of commercially available antibody Cetuximab against EGFR and monoclonal antibody mF4-31C1 against VEGFR-3 in nude mice, xenografted intraperitoneally with SKOV-3m human ovarian carcinoma cell line. 111-Indium labeled antibodies were injected intravenously and the biodistribution was followed for three days using combined SPECT/CT imaging.

Results Biodistribution studies showed that both antibodies accumulated to the peritoneal tumor area up to three days of which Cetuximab had lower liver tropism and faster tumor homing rate compared to mF4-31C1. In addition, on the third day two out of five tumor bearing mice showed clear accumulation of the In-labeled mF4-31C1 at the left axillary area, indicating the increase of VEGFR-3 expression in those lymph nodes compared to healthy cotrol animals which was also confirmed by immunohistological staining.

Conclusions These results suggest that both Cetuximab and mF4-31C1 are potential diagnostic tools for SPECT/CT imaging of human ovarian carcinoma.