Pustaka Ilmiah Universitas Padjadjaran

Abstrak

Synthesis and stability test of radiogadolinium(III)DOTA-PAMAMG3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2positive breast cancer

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)-DOTAPAMAM G3.0-trastuzumab in the form of 147 Gd-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. 147 Gd radionuclide emits g-rays that can be used in SPECT modality, but because of technical constraint, Gd radionuclide was simulated by its radioisotope, 153 Gd. 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 153 Gd. 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 2e8 0C as indicated by its radiochemical purity 97.6 ± 0.5%e99.1 ± 0.5% after 144 h storage.