title: A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab.
abstract: In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with (177)Lu 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 (177)Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours. DOTA-Nimotuzumab was radiolabeled with (177)LuCl3 (15 MBq/mg) at 37°C 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 (177) LuCl(3) 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 (177)Lu-DOTA-Nimotuzumab was observed in A431 cell binding studies. Biodistribution studies demonstrated increasing tumor uptake of (177)Lu-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. (177)Lu-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.
authors.affiliation: Laboratorio de Radiofarmacia, CIN, Montevideo, Uruguay.
authors.forename: Victoria
authors.initials: V
authors.lastname: Calzada
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.forename: Arlhee
authors.initials: A
authors.lastname: Diaz-Miqueli
authors.forename: Normando
authors.initials: N
authors.lastname: Iznaga-Escobar
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
authors.forename: Henia
authors.initials: H
authors.lastname: Balter
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004355:Drug Stability; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015282:Octreotide / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C501466:nimotuzumab; C447941:lutetium Lu 177 dotatate; D066246:ErbB Receptors; D015282:Octreotide