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  • Artigo IPEN-doc 28072
    Radioimmunotheranostic pair based on the anti-HER2 monoclonal antibody
    2021 - MIRANDA, ANA C.C.; SANTOS, SOFIA N. dos; FUSCALDI, LEONARDO L.; BALIEIRO, LUIZA M.; BELLINI, MARIA H.; GUIMARAES, MARIA I.C.C.; ARAUJO, ELAINE B. de
    The oncogene HER2 is an important molecular target in oncology because it is associated with aggressive disease and the worst prognosis. The development of non-invasive imaging techniques and target therapies using monoclonal antibodies is a rapidly developing field. Thus, this work proposes the study of the radioimmunotheranostic pair, [111In]In-DTPA-trastuzumab and [177Lu]Lu-DOTA-trastuzumab, evaluating the influence of the chelating agents and radionuclides on the biological properties of the radioimmunoconjugates (RICs). The trastuzumab was immunoconjugated with the chelators DTPA and DOTA and radiolabeled with [111In]InCl3 and [177Lu]LuCl3, respectively. The stability of the RICs was evaluated in serum, and the immunoreactive and internalization fractions were determined in SK-BR-3 breast cancer cells. The in vivo pharmacokinetics and dosimetry quantification and the ex vivo biodistribution were performed in normal and SK-BR-3 tumor-bearing mice. The data showed that there was no influence of the chelating agents and radionuclides on the immunoreactive and internalization fractions of RICs. In contrast, they influenced the stability of RICs in serum, as well as the pharmacokinetics, dosimetry and biodistribution profiles. Therefore, the results showed that the nature of the chelating agent and radionuclide could influence the biological properties of the radioimmunotheranostic pair.
  • Artigo IPEN-doc 27742
    Anti-HER2 monoclonal antibody based-radioimmunoconjugates
    2021 - MIRANDA, ANA C.C.; DURANTE, ANA C.R.; FUSCALDI, LEONARDO L.; BARBEZAN, ANGELICA B.; LIMA, CILENE R. de; PERINI, EFRAIN; ARAUJO, ELAINE B. de
    In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical–chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator 􀀀 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.
  • Artigo IPEN-doc 26649
    Comparative overview of innovation and patent filings in Radiopharmacy
    2020 - MIRANDA, ANA C.C.; LOBATO, DENISE R.; ARAUJO, ELAINE B. de
    Objective: To expose the current situation of the Brazilian Nuclear Medicine in relation to innovation, taking into account the Intellectual Property protection and the particularities of this field. Methods: The number and the origin of patents filings from Brazil, United States and European Patent Convention countries were retrospectively compared in a 20-year period. Results: The number of accumulated patents filings of conventional pharmaceuticals was ten times higher compared to the radiopharmaceuticals in the three regions studied. Conclusion: The largest number of Brazilian patents filings corresponded to the international patent applications, which is related to the country development conditions, as well as to the difficulties in the process of patent filing.
  • Artigo IPEN-doc 01937