Preclinical validation of 111In-girentuximab-F(ab')2 as a tracer to image hypoxia related marker CAIX expression in head and neck cancer xenografts
SourceRadiotherapy and Oncology, 124, 3, (2017), pp. 521-525
Article / Letter to editor
Display more detailsDisplay less details
Radiotherapy and Oncology
SubjectRadboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
BACKGROUND AND PURPOSE: Hypoxia is a major cause of radio- and chemoresistance. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker and an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment. The radioactive tracer 111In-girentuximab-F(ab')2 targets CAIX and can be used for SPECT imaging. Aim of this study was to validate and optimize 111In-girentuximab-F(ab')2 for imaging of CAIX expression in head and neck tumor xenografts. MATERIAL AND METHODS: Affinity and internalization kinetics of 111In-girentuximab-F(ab')2 were determined in vitro using CAIX-expressing SK-RC-52 cells. Tumor targeting characteristics were determined in athymic mice with six different head and neck squamous cell carcinoma (SCCNij) xenografts. Tracer uptake was measured by ex vivo radioactivity counting. Intratumoral distribution of tracer uptake was measured using autoradiography and CAIX expression was determined immunohistochemically. RESULTS: 26% of the tracer was internalized into the SK-RC-52 cells within 24h. The half maximal inhibitory concentration (IC50) was 0.69+/-0.08nM. In biodistribution studies SCCNij153 tumors showed the highest tracer uptake: 4.1+/-0.8ID/g at 24h p.i. Immunohistochemical and autoradiographic analyses of the xenografts showed a distinct spatial correlation between localization of the tracer and CAIX expression. CONCLUSION: 111In-girentuximab-F(ab')2 has a high affinity for CAIX. In vivo tumor uptake correlated strongly with CAIX expression in different head and neck xenografts. These results suggest that 111In-girentuximab-F(ab')2 is a promising tracer for imaging of hypoxia-related CAIX expression.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.