Radiolabeled F(ab')2 -cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
P-S BellayeB Collin

Abstract

This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111In and 177Lu, respectively. We designed F(ab')2-fragments of cetuximab radiolabeled with 111In and 177Lu. 111In-F(ab')2-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111In-F(ab')2-cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177Lu-F(ab')2-cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Radiolabeling procedure did not change F(ab')2-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111In-DOTAGA-F(ab')2-cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab')2-cetuximab. SPECT imaging of 111In-DOTAGA-F(ab')2-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease...Continue Reading

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BETA
biopsy
FACS

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InVivoScope
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