In vivo SPECT/CT imaging of human orthotopic ovarian carcinoma xenografts with 111In-labeled monoclonal antibodies.
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 3 (VEGFR-3) are expressed in the tumor area during the progression of ovarian carcinoma. Monoclonal antibodies developed against these receptors are potential diagnostic molecules for in vivo imaging of ovarian carcinoma.


METHODS
Biodistribution of the monoclonal antibodies cetuximab against EGFR and mF4-31C1 against VEGFR-3 was studied in nude mice with orthotopic SKOV-3m human ovarian carcinoma xenografts. The biodistribution of (111)Indium-labeled antibodies was followed up to 48 h postinjection using combined SPECT and CT imaging modality. Organ samples were collected postmortem and specific organ activity was measured. Accumulation of the intravenously injected antibodies in the tumor tissue and lymph nodes was verified using immunohistology.


RESULTS
Imaging studies with SPECT/CT showed clear accumulation of both antibodies into tumor area. The tumor uptake was 8.78 ± 0.74 %ID/g for cetuximab and 5.77 ± 0.62 %ID/g for mF4-31C1 after 48 h postinjection. Cetuximab had lower liver tropism and faster tumor homing rate. In addition, after 48 h two of five tumor-bearing mice showed a clear accumulation of the In-labeled mF4-31C1 at the left axillary area. Both intravenously administered antibodies could also be detected from the tumor sections by immunohistological staining but only mF4-31C1 forms in the lymph nodes.


CONCLUSIONS
These results demonstrate the accumulation of EGFR- and VEGFR-3-specific antibodies in orthotopic ovarian carcinoma tumors. Systemically administered they had slow pharmacokinetics which is typical for antibodies. Accumulation of mF4-31C1 antibody in the lymph nodes suggests the remote activation of VEGFR-3 by the primary tumor.
Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Finland.
Tuulia
T
Huhtala
Pirjo
P
Laakkonen
Hanna
H
Sallinen
Seppo
S
Ylä-Herttuala
Ale
A
Närvänen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D017209:Apoptosis; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D007267:Injections; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D066246:ErbB Receptors; D040321:Vascular Endothelial Growth Factor Receptor-3