期刊
JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES
卷 8, 期 1, 页码 91-99出版社
TAYLOR & FRANCIS LTD
DOI: 10.1016/j.jrras.2014.12.001
关键词
Gd-DOTA-PAMAM G3.0-trastuzumab; HER-2; Target-specific radiopharmaceutical; Targeted contrast agent
资金
- Radioisotopes and Radiopharmaceuticals Technology Centre, National Nuclear Energy Agency of Indonesia
Nonivasive diagnosis of cancer can be provided by molecular imaging using hybrid modality to obtain better sensitivity, specificity and depiction localization of the disease. In this study, we developed a new molecular imaging agent, radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab in the form of Gd-147-DOTA-PAMAM G3.0-trastuzumab, that can be both target-specific radiopharmaceutical in SPECT as well as targeted contrast agent in MRI for the purpose of diagnosis of HER-2 positive breast cancer. (14)7Gd radionuclide emits gamma-rays that can be used in SPECT modality, but because of technical constraint, Gd-147 radionuclide was simulated by its radioisotope, Gd-153. Gd-DOTA complex has also been known as good MRI contrast agent. PAMAM G3.0 is useful to concentrate Gd-DOTA compelexes in large quantities, thus minimizing the number of trastuzumab molecules used. Trastuzumab is human monoclonal antibody that can spesifically interact with HER-2. Synthesis of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was initiated by conjugating DOTA NHS ester ligand with PAMAM G3.0 dendrimer. The DOTA-PAMAM G3.0 produced was conjugated to trastuzumab molecule and labeled with 153Gd. Characterization DOTA-PAMAM G3.0-trastuzumab immunoconjugate was performed using HPLC system equipped with SEC. The formation of immunoconjugate was indicated by the shorter retention time (6.82 min) compared to that of trastuzumab (7.06 min). Radiochemical purity of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab was > 99% after purification process by PD-10 desalting column. Radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab compound was stable at room temperature and at 2-8 (OC) as indicated by its radiochemical purity 97.6 +/- 0.5%-99.1 +/- 0.5% after 144 h storage. Copyright (C) 2014, The Egyptian Society of Radiation Sciences and Applications. Production and hosting by Elsevier B. V. This is an open access article under the CC BY-NC-ND license.
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