Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive 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)-DOTA-PAMAM G3.0-trastuzumab in the form of 14...
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doaj-0be44bc6e1e142d7a9edf5a84c7512f72020-11-25T00:59:48ZengTaylor & Francis GroupJournal of Radiation Research and Applied Sciences1687-85072015-01-0181919910.1016/j.jrras.2014.12.001Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancerHardiani Rahmania0Abdul Mutalib1Martalena Ramli2Jutti Levita3Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Jawa Barat, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Jawa Barat, IndonesiaRadioisotopes and Radiopharmaceuticals Technology Centre, National Nuclear Energy Agency of Indonesia, Kawasan PUSPIPTEK, South Tangerang, Banten, IndonesiaDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Jawa Barat, IndonesiaNonivasive 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 147Gd-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. 147Gd radionuclide emits γ-rays that can be used in SPECT modality, but because of technical constraint, 147Gd radionuclide was simulated by its radioisotope, 153Gd. 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 0C as indicated by its radiochemical purity 97.6 ± 0.5%–99.1 ± 0.5% after 144 h storage.http://www.sciencedirect.com/science/article/pii/S168785071400123XGd-DOTA-PAMAM G3.0-trastuzumabHER-2Target-specific radiopharmaceuticalTargeted contrast agent |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hardiani Rahmania Abdul Mutalib Martalena Ramli Jutti Levita |
spellingShingle |
Hardiani Rahmania Abdul Mutalib Martalena Ramli Jutti Levita Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer Journal of Radiation Research and Applied Sciences Gd-DOTA-PAMAM G3.0-trastuzumab HER-2 Target-specific radiopharmaceutical Targeted contrast agent |
author_facet |
Hardiani Rahmania Abdul Mutalib Martalena Ramli Jutti Levita |
author_sort |
Hardiani Rahmania |
title |
Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer |
title_short |
Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer |
title_full |
Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer |
title_fullStr |
Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer |
title_full_unstemmed |
Synthesis and stability test of radiogadolinium(III)-DOTA-PAMAM G3.0-trastuzumab as SPECT-MRI molecular imaging agent for diagnosis of HER-2 positive breast cancer |
title_sort |
synthesis and stability test of radiogadolinium(iii)-dota-pamam g3.0-trastuzumab as spect-mri molecular imaging agent for diagnosis of her-2 positive breast cancer |
publisher |
Taylor & Francis Group |
series |
Journal of Radiation Research and Applied Sciences |
issn |
1687-8507 |
publishDate |
2015-01-01 |
description |
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 147Gd-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. 147Gd radionuclide emits γ-rays that can be used in SPECT modality, but because of technical constraint, 147Gd radionuclide was simulated by its radioisotope, 153Gd. 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 0C as indicated by its radiochemical purity 97.6 ± 0.5%–99.1 ± 0.5% after 144 h storage. |
topic |
Gd-DOTA-PAMAM G3.0-trastuzumab HER-2 Target-specific radiopharmaceutical Targeted contrast agent |
url |
http://www.sciencedirect.com/science/article/pii/S168785071400123X |
work_keys_str_mv |
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