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Journal of Cancer Research and Clinical Oncology

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08-04-2023 | Cetuximab | Research

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

Authors: Seyed Mohammad Hosseini, Javad Mohammadnejad, Hassan Yousefnia, Behrouz Alirezapour, Ali Hossein Rezayan

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2023

Abstract

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.

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Title: Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate
Authors: Seyed Mohammad Hosseini
Javad Mohammadnejad
Hassan Yousefnia
Behrouz Alirezapour
Ali Hossein Rezayan
Publication date: 08-04-2023
Publisher: Springer Berlin Heidelberg
Keyword: Cetuximab
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-04724-z

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