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

Purpose: 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, In and Lu, respectively.

Methods: We designed F(ab')-fragments of cetuximab radiolabeled with In and Lu. In-F(ab')-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of In-F(ab')-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 Lu-F(ab')-cetuximab was evaluated in SWISS nude mice bearing A431 tumors.

Results: Radiolabeling procedure did not change F(ab')-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. In-DOTAGA-F(ab')-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')-cetuximab. SPECT imaging of In-DOTAGA-F(ab')-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, Lu-DOTAGA-F(ab')-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses.

Conclusions: In-DOTAGA-F(ab')-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. Lu-DOTAGA-F(ab')-cetuximab is an interesting theranostic tool allowing therapy and imaging.