Radiolabeled F(ab′)(2)-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, (111)In and (177)Lu, respectively. METHODS: We designed F(ab′)(2)-fragments of cetuximab radiolabeled with (111)In and (177)Lu. (111)In-F(ab′)(2)-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of (111)In-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 (177)Lu-F(ab′)(2)-cetuximab was evaluated in SWISS nude mice bearing A431 tumors. RESULTS: Radiolabeling procedure did not change F(ab′)(2)-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. (111)In-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 (111)In-DOTAGA-F(ab′)(2)-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, (177)Lu-DOTAGA-F(ab′)(2)-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. CONCLUSIONS: (111)In-DOTAGA-F(ab′)(2)-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. (177)Lu-DOTAGA-F(ab′)(2)-cetuximab is an interesting theranostic tool allowing therapy and imaging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12094-018-1886-4) contains supplementary material, which is available to authorized users.