A Potencial Theranostic Agent for EGF-R Expression Tumors: 177Lu- DOTA-Nimotuzumab

Victoria      Calzada; Xiuli      Zhang; Marcelo      Fernandez; Arlhee      Diaz-Miqueli; Normando      Iznaga-Escobar; Susan      L. Deutscher; Henia      Balter; Thomas      P. Quinn; Pablo      Cabral

Abstract

In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with 177Lu as a potential cancer therapy radiopharmaceutical. In-vitro cell binding studies and in-vivo biodistribution and imaging studies were performed to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours. DOTA-Nimotuzumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37ºC for 1 h. The radiochemical purity was assessed by ITLC, silica gel and by RP-HPLC. Binding specificity studies were performed with EGF-R positive A431 human epithelial carcinoma and EGF-R negative MDA-MB-435 breast carcinoma cells. Biodistribution studies were performed in healthy female CD-1 mice at 1 h, 4 h, 24 h, and A431 xenografted nude mice at 10 min, 1 h, 4 h, 24 h, 48 h, and 96 h. SPECT-CT imaging studies were performed in A431 xenografted mice at 24 h post injection. DOTA-Nimotuzumab was efficiently labeled with 177LuCl3 at 37°C. The in vitro stability of labeled product was optimal over 24 h in buffered saline and mouse serum. Specific recognition of EGF-R by 177Lu-DOTA-Nimotuzumab was observed in A431 cell binding studies. Biodistribution studies demonstrated increasing tumor uptake of 177Lu-DOTA-Nimotuzumab over time, with tumor to muscle ratios of 6.26, 10.68, and 18.82 at 4 h, 24 h, and 96 h post injection. Imaging of A431 xenografted mice showed high uptake in the tumor. 177Lu-DOTA-Nimotuzumab has the potential to be a promising therapy agent, which may be useful in the treatment of patients with EGF-R positive cancer.

Keywords: EGFR, Nimotuzumab, DOTA, 177Lu, cancer.

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