Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate.

Purpose: Epidermal growth factor receptors (EGFRs) are overexpressed in a wide range of tumors and are attractive candidates to target in targeted therapies. This study aimed to introduce a novel radiolabeled compound, ¹⁷⁷Lu-cetuximab-PAMAM G4, for the treatment of EGFR-expressing tumors. Methods: In this study, the cetuximab mAb was bound to PAMAM G4 and labeled with ¹⁷⁷Lu via DTPA-CHX chelator. The synthesized nanosystem was confirmed by different analyses such as DLS, FT-IR, TEM, and RT-LC. Cell viability of the radioimmunoconjugate was assessed over the EGFR-expressing cell line of SW480. The biodistribution of ¹⁷⁷Lu-Cetuximab-PAMAMG4 was determined in different intervals after injection of the radiolabeled compound in normal and tumoral nude mice via scarification and SPECT images. Results: The average size of PAMAM G4 and PAMAM-Cetuximab-DTPA-CHX nanoparticles were 2 and 70 nm, respectively. ¹⁷⁷Lu-Cetuximab-PAMAMG4 was prepared with radiochemical purity of more than 98%. The survival rates of SW480 cells at 24, 48, and 72 h post-treatment with¹⁷⁷Lu-Cetuximab-PAMAMG4 (500 nM) were 18%, 15%, and 14%, respectively. The biodistribution studies showed a significant accumulation of ¹⁷⁷Lu-Cetuximab-PAMAM in the EGFR-expressing tumor. Conclusion: According to the results, this new agent can be considered as an efficient therapeutic complex for tumors expressing EGFR receptors. [ABSTRACT FROM AUTHOR]