2024 - SILVA, CAMILA R.; KAYANI, ZAHRA; RIBEIRO, MARTHA S.; BERIONNI, GUILLAUME; HEUSKIN, ANNE-CATHERINE

Triple-negative breast cancer (TNBC) is a subtype of the breast cancer that represents around 20% of all invasive breast cancer, which main characteristics is resistance to conventional treatments, such as exposure to ionizing radiation (IR). On the order hand, photodynamic therapy (PDT) using porphyrins has been described in the literature as a potential therapy against cancer and currently with the advance of nanomedicine, nanoparticles (NPs) have been used to deliver the photosensitizer with greater precision mainly in deep tumor. Thus, our goal in this work was to develop a NP coated with TMPyP and associate it with IR in the treatment of TNBC.

2023 - SOUZA, F.V.; SILVA, F.F.A.; ARAUJO, P.H.S.; BERNARDES, E.S.

Introdução: Trastuzumab IgG1 binds to the HER2 receptor on cancer cells, inhibiting the growth signal and stimulating the immune system to combat them. Its use in therapy has been employed for HER2-positive breast cancer. Advances in nuclear medicine have enabled the development of radiopharmaceuticals for its diagnosis, consisting of a radionuclide, a molecule that binds to the specific target, and a marker that allows visualization of cancer cells through μPET/SPECT/CT. The 99m -Tc isotope is used in nuclear medicine due to its suitable half-life for obtaining images, low concentrations of the isotope, and short half-life. Trastuzumab therapy has shown efficacy in HER2+ tumors, while radiopharmaceuticals play an important role in breast cancer screening. Objetivos: The objective is to obtain a specific radiopharmaceutical for the HER2-positive receptor capable of diagnosing breast tumors with high sensitivity and specificity. Métodos: The methodology involves the preparation of the Trastuzumab antibody conjugated to the radioactive isotope 99m -Tc, conjugated with HYNIC-NHS and DMSO under 60 minutes of agitation. It is then purified with C?H?NO?, followed by the addition of 0.1 mg of Sn 2 Cl in 5μL of HCl, 1 mg of C 6 H 13 NO 5 , and 1 mg of C 2 H 4 (NHCH 2 CO2H)2 in 100 μL of C?H?NO?, and 8mCi of 99m -Tc. After incubation, the sample is washed with PBS, and the product yield is confirmed by CCD. The stability test was performed to observe the influence of external factors. Trastuzumab- 99m -Tc was added to mouse saline and plasma at 37ºC and analyzed at 15 minutes, 1, 2, 3, 4, 5, 6, and 24 hours using CCD on the Y counter. The experiments were conducted in accordance with the approved local ethics committee (CEUA: nº30/22). Eight-week-old female Balb/c nude mice were subcutaneously inoculated with 1X106 SKBR3 cells (ATTC: HTB30- Positive for HER2) and 1x106 MDA-MB-231 ATTC: HTB-26 - Negative for HER2). The radiolabeling using Trastuzumab, HYNIC, and 99m -Tc showed aradiochemical purity of ? 95%. Resultados: The radiolabeling using Trastuzumab, HYNIC, and 99m -Tc showed a radiochemical purity of ? 95%. The stability study conducted in saline and plasma demonstrated that Trastuzumab- 99m -Tc is stable for up to 24 hours with a radiochemical purity of ? 95%. Conclusão: In conclusion, it has been determined that the radiolabeling of Trastuzumab-99m-Tc is feasible and stable for up to 24 hours. The next step is the study of cellular internalization and in vitro immunoreactivity, followed by biodistribution in animals with HER2-positive tumors when they reach a size of 0.3 cm3, using Trastuzumab-99m-Tc.

2024 - TERZER-WASSMUTH, STEFAN; ARAGUAS-ARAGUAS, LUIS; WASSENAAR, LEONARD I.; MONTEIRO, LUCILENA R.; STUMPP, CHRISTINE

During the past decade, the rare O isotope 17O and the 17O-excess became attractive for potential new applications in hydrology, climatology, and broader oxygen isotope research. Although laser-based analysers are technologically capable of the needed Δ′17O assays, progress was hindered by the metrological challenges and the absence of fundamental spatiotemporal data on precipitation inputs. Uncertainties surrounding the input function of the water cycle complicate advancements of 17O as a tracer. This “emerging tracer dilemma” is a potential obstacle for further triple-O isotope research. In this work, >3500 archived water samples from the Global Network of Precipitation (GNIP) sample archives (2015-2021) were re-analysed for for δ17O and Δ′17O. For >60 GNIP stations, four or more years’ of samples were analysed, assessing the seasonality of Δ′17O, and constructing δ17O/ δ18O Local Meteoric Water Lines (LMWL). This global dataset allowed for a first-ever comprehensive assessment of the spatial patterns of δ17O/ δ18O LMWLs, and to devise a first-ever precipitation-weighted Global Meteoric Water Line (GMWL): δ′17O = 0.5280 ± 0.0002 δ′18O + 0.0153 ± 0.0013. This GMWL definition is similar to previous efforts albeit with a lower ordinate intercept. We further analysed the Δ′17O of a 6-year daily/fortnightly precipitation sampling in Vienna as an example of seasonal isotopic variations at synoptic weather patterns’ resolution. Air moisture sources were determined by backwards trajectory analysis and corroborated with synoptic weather data from Austria’s meteorological service. The Δ′17O values correlated with δ18O seasonality. A comparison with the deuterium excess patterns (stemming from the Atlantic and Mediterranean domains) demonstrated that the “two excesses” carried different signals. While elevated d-excesses mainly came from the central/eastern Mediterranean Sea or easterly continental sources during all seasons, we found elevated Δ′17O precipitation originated only from northerly or north-easterly sources, and predominantly during the winter season. Finally, we present pilot Vienna precipitation events sampled at sub-hourly (to 5-minute) resolution, which included both cyclonic and convective rainfall events, which demonstrate the interplay of moisture sources using triple oxygen isotopes and deuterium excess. This work will help to shape our understanding of δ17O and Δ′17O in Earth’s precipitation, despite the ongoing metrological challenges faced, and promote discussion regarding the scientific value of routine measurements for triple-oxygen isotopes in precipitation.

2023 - GARCIA, VANESSA S.G.; TALLARICO, LENITA de F.; GUIMARAES, MARIA C.F.; NAKANO, ELIANA; BORRELY, SUELI I.

Os surfactantes são exemplos de compostos críticos contidos em efluentes industriais e domésticos devido à sua persistência, elevado teor de matéria orgânica e de fósforo e por causar efeitos deletérios à biota aquática. Além disso, a espuma formada em corpos hídricos devido à presença de surfactantes altera parâmetros importantes da qualidade da água, reduzindo a capacidade de biodegradação e trocas gasosas, contribuindo para o florescimento de algas e influenciando a solubilidade de contaminantes orgânicos. Devido a sua complexidade, remover surfactantes de efluentes tem sido uma questão fundamental. Neste contexto, os Processos Oxidativos Avançados vêm sendo utilizados para melhorar a tratabilidade desse tipo de contaminante, complementando o tratamento biológico. A irradiação por feixe de elétrons vem sendo estudada como mais uma possibilidade tratamento de efluentes. Este estudo avaliou os efeitos agudos do surfactante aniônico – Linear Aquilbenzeno Sulfonado (LAS) antes e após o tratamento com feixe de elétrons. Nos ensaios ecotoxicológicos foram empregados: Vibrio fischeri (bactéria luminescente), Daphnia similis (cladocera) e Biomphalaria glabrata (molusco). O surfactante LAS foi submetido à irradiação em acelerador de elétrons, nas doses de 2,5 kGy e 5 kGy. Da exposição aguda ao LAS, D. similis foi o organismo mais sensível (CE50 = 9,52 mg/L ± 0,43), seguido por B. glabrata (CL50=19,17 mg/L) e de V. fischeri (CE50 = 29,54 mg/L ± 0,57). Os resultados de toxicidade obtidos após tratamento do surfactante LAS com feixe de elétrons foram promissores, com significativa eficiência na redução da toxicidade para os organismos D. similis e V. fischeri: acima de 45% - 2,5 kGy e 70% - 5kGy. A proposta da abordagem ecotoxicológica de surfactantes fornece informações relevantes sobre o comportamento destes poluentes perigosos em corpos hídricos frente à biota aquática, permitindo avaliar os impactos de surfactantes no ecossistema aquático. Assim, os dados de toxicidade são importante ferramenta de avaliação também sobre a eficácia do tratamento proposto e podem ser associados a planos de gestão e tratamento adequados desse grupo de contaminantes.