Evaluation of 177Lu-nimotuzumab for Targeted Radioimmunotherapy of EGFR Expressing Tumors

0385312 - ÚJF 2013 US eng A - Abstrakt
Beckford, Denis R. - Balogh, L. - Postenyi, Z. - Mathe, D. - Eigner, Sebastian - Eigner-Henke, Kateřina - Montana, R. L. - Melichar, František
Evaluation of 177Lu-nimotuzumab for Targeted Radioimmunotherapy of EGFR Expressing Tumors.
European Journal of Nuclear Medicine and Molecular Imaging. Springer. Roč. 39, P0089 (2012), S327-S327. ISSN 1619-7070. E-ISSN 1619-7089.
[25th Annual Congress of the European-Association-of-Nucelar Medicine. 27.10.2012-31.10.2012, Milan]
Institucionální podpora: RVO:61389005
Klíčová slova: radiotherapy * tumor treatment
Kód oboru RIV: BG - Jaderná, atomová a mol. fyzika, urychlovače

Nimotuzumab radiolabeled with 99mTc and 188Re has been successfully used for imaging and therapy of EGFR overexpressing tumors in clinical trials. 177Lu is being strongly considered for radioimmunotherapy due to its excellent nuclear properties and suitability for imaging and dosimetry determination. Therefore, the aim of this work was to evaluate the therapeutic effect of 177Lu-nimotuzumab in a tumor animal model. Methods: Nimotuzumab was modified with p-SCN-Bn-DOTA and radiolabeled with n. c. a. 177Lu. The radioimmunoconjugate was characterized by size exclusion radio-HPLC. Specificity and affinity were tested using radioimmunoassays in a cell line overexpressing EGFR. Radioimmunotherapy study was performed in BALB/c-nu mice bearing human A431 and MCF-7 xenografts. Mice were divided in four groups and 177Lu-nimotuzumab (15 - 45 MBq/mouse) was intravenously administered. The effect in tumor growth and survival after single injection of 177Lu-nimotuzumab was studied. In addition, the ratio in tumor uptake between A431 and MCF-7 tumors was also studied. Results: Radiochemical yield and specific activity of 177Lu-Nimotuzumab were higher than 95% and 1.3 GBq/mg, respectively. The binding of 177Lu-nimotuzumab to A431 cells showed to be EGFR specific. A single dose of 177Lu-nimotuzumab (15 - 45 MBq/mouse) reduces tumor growth in A431 and MCF-7 tumors after 3 weeks of treatment. Tumor volume was 3.7 to 4.3 times higher in MCF-7 tumors than in A431 xenografts after 6 weeks of treatment. The tumor uptake of 177Lu-nimotuzumab in A431 tumors was 1.4 to 2.1 times higher than in MCF-7 tumors. The survivals were statistically different among the groups. No death occurred in the group treated with 15 MBq of 177Lu-nimotuzumab. Conclusions: The results showed the therapeutic effect of 177Lu-nimotuzumab to be potential for radioimmunotherapy of EGFR overexpressing tumors.
Trvalý link: http://hdl.handle.net/11104/0216893