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In Vitro and In Vivo Testing of 177Lu-DOTA-Nimotuzumab, a Potential Radioimmunotherapeutical Agent of Cancers
Martalena Ramli1, Basuki Hidayat2, Cecep Taufik Rustendi1, Muhammad Subur1, Cahya Nova Ardiyatno1, Karyadi1, Sri Aguswarini1, Titis Sekar Humani1, Rien Ritawidya1, Abdul Mutalib1 & Johan S. Masjhur2
1Radioisotopes and Radiopharmaceuticals Centre, National Nuclear Energy Agency of Indonesia, Kawasan PUSPIPTEK Gd. 11 Serpong, Tangerang Selatan 15310
2Department of Nuclear Medicine and Molecular Imaging, School of Medicine, Padjadjaran University/Dr. Hasan Sadikin General Hospital,
Jl. Pasir Kaliki No. 192, Bandung 40161
E-mail: marta_r@batan.go.id
Abstract. Nimotuzumab is an anti-cancer agent that belongs to the inhibitor group of anti-epidermal growth factor receptors (EGFR). This antibody inhibits the EGF protein receptor, which is over-expressed on cancer cells in cancers such as colorectal, brain, pancreas, prostate, non-small cell lung, oesophagus, cervical and breast cancer. In order to obtain a higher efficacy agent for therapy of the above-mentioned cancers, nimotuzumab was labeled with beta particle- and gamma-emitter 177Lu. This report discusses the results of our in vitro and in vivo tests, which included cytotoxicity, clearance, imaging and biodistribution tests. The cytotoxicity test of 177Lu-DOTA-nimotuzumab on A 549 cell lines (lung carcinoma) was found to kill more cancer cells compared to that of unradiolabeled nimotuzumab. The clearance test of 177Lu-DOTA-nimotuzumab on normal rats showed that the residues of radioactivity were excreted mostly via the urine. The biodistribution and image tests showed that post injection of 177Lu-DOTA-nimotuzumab there was still some radioactivity in a number of organs, such as the kidney, liver and bone. Although the state of radioactivity post injection of 177Lu-DOTA-nimotuzumab in the above-mentioned organs was nearly the same as or slightly lower compared to other radiolabeled monoclonal antibodies, precautions still have to be observed when this product is going to be tested on cancer patients.
Keywords: Anti EFGR radiolabeled monoclonal antibody; in vitro; in vivo tests; 177Lu-DOTA-nimotuzumab.
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