LUIS ALBERTO PEREIRA DIAS
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Artigo IPEN-doc 29639 Development of glycan‑targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatment2023 - SANTOS, SOFIA N. dos; GUSHIKEN JUNIOR, DINO S.; PEREIRA, JHONATAS P.M.; IADOCICCO, NATALIA M.; SILVA, ANDRE H.; NASCIMENTO, TATIELLE do; DIAS, LUIS A.P.; SILVA, FLAVIA R. de O.; RICCI-JUNIOR, EDUARDO; SANTOS-OLIVEIRA, RALPH; BERNARDES, EMERSON S.Chemotherapy resistance remains a major cause of therapeutic failure in gastric cancer. The combination of genetic material such as interference RNAs (iRNAs) to silence cancer-associated genes with chemotherapeutics has become a novel approach for cancer treatment. However, finding the right target genes and developing non-toxic, highly selective nanocarrier systems remains a challenge. Here we developed a novel sialyl-Tn-targeted polylactic acid—didodecyldimethylammonium bromide nanoparticle (PLA-DDAB) nanoparticles (NPs) loaded with dsRNA targeting ST6GalNac-I and/or galectin-3 genes. Using single photon emission computed tomography (SPECT), we have demonstrated that 99mtechnetium radiolabeled sialyl-Tn-targeted nanoparticles can reach the tumor site and downregulate ST6GalNAc-I and galectin-3 RNA expression levels when injected intravenously. Furthermore, using an in vivo gastric tumor model, these nanoparticles increased the effectiveness of 5-FU in reducing tumor growth. Our findings indicate that cancer-associated glycan-targeted NPs loaded with dsRNA targeting ST6GalNAc-I and/or galectin-3 in combination with standard chemotherapy, have the potential to become a novel therapeutic tool for gastric cancer.Artigo IPEN-doc 28654 In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-1772022 - BOAS, CRISTIAN A.W.V.; SILVA, JEFFERSON de J.; DIAS, LUIS A.P.; FREIRE, MARIA R.B.; BALIEIRO, LUIZA M.; SANTOS, CAROLINA S.F. dos; VIVALDINI, BIANCA F.; BENEDETTO, RAQUEL; VIEIRA, DANIEL P.; PASSOS, PRISCILA de Q.S.; MARUMO, MARIA H.; TEIXEIRA, LUIS F.S.; ARAUJO, ELAINE B. deThe PSMA-targeted radionuclide therapy has been explored since 2015 with radioisotope lutetium-177, whose β− emission range is adequate for micrometastases treatment. This radioisotope is obtained by two different production routes that directly affect the specific activity of lutetium-177 (non-carrier added and carrier added) and, consequently, the specific activity of radiopharmaceuticals, like 177Lu-PSMA-617. The influence of the specific activity of lutetium-177 on the properties of the radiopharmaceutical PSMA-617 was evaluated through pre-clinical studies. The in vitro study pointed to a lower constant of dissociation with non-carrier added lutetium-177 due to the difference in the specific activity. However, competition and internalization assays resulted in similar results for both lutetium-177. Based on these pre-clinical experiments, the total in vitro tumor cell binding and tumor uptake in vivo were similar, with no influence of the specific activity of the 177Lu-PSMA-617. Regardless the specific activity did not directly affect tumor uptake, the tumor/non-target organs ratios were higher for the radiopharmaceutical labeled with carrier added lutetium-177, which had the lowest specific activity.Artigo IPEN-doc 27848 Stability in production and transport of 177Lu labeled PSMA2021 - VILLAS BOAS, C.A.W.; DIAS, L.A.P.; MATSUDA, M.M.N.; ARAUJO, E.B.In Brazil, prostate cancer is a common disease among men. The radionuclide therapy with PSMA analogs, labeled with beta and alpha emitters, has brought new perspectives for patients with multi metastatic resistant prostate cancer. The commercialization of radiopharmaceutical becomes a challenge to transport and ensure the quality of the product, especially in terms of radiochemical stability of therapeutic radiopharmaceuticals. The effect of radiolysis on therapeutic doses of radiopharmaceuticals can be avoided or mitigated by diluting the final dose and reducing storage and transportation temperature. This study evaluated the effect of radiolysis on the different radioactive concentration in the industrial batches of 177Lu-PSMA-617 and in the fractionated doses, considering long time transportation. The radiopharmaceutical 177Lu-PSMA-617 was produced in batches reaching 37 GBq, and stability studies were performed in controlled conditions. The results showed that a combination of factors, including reaction buffer, the radioactive concentration of final product, and freezing storage contributed to the stability of the radiopharmaceutical for 48 hours, enabling transport of 177Lu-PSMA-617 to distant regions of the country.Artigo IPEN-doc 21020 Optimization of labelling PSMA-HBED-CC peptide with sup(68)Ga2015 - ALCARDE, LAIS F.; DIAS, LUIS A.P.; MASSICANO, ADRIANA V.F.; MENGATTI, JAIR; ARAUJO, ELAINE B. de