FABIO LUIZ NAVARRO MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Repeatability of brown adipose tissue activation measured by [18F]FDG PET after beta3-adrenergic stimuli in a mouse model(2023) FARIA, Daniele de Paula; VERA, Cleinando Clemente da Silva; MARQUES, Fabio Luiz Navarro; SAPIENZA, Marcelo TatitThis study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [F-18]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice.Methods: Male C57BL/6 mice underwent [F-18]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective beta 3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test.Results: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation.Conclusions: The study demonstrated that administration of the selective beta 3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [F-18]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.
article 0 Citação(ões) na Scopus Patentometric analysis as a subsid to the management of technological innovation: a case study in radiopharmaceuticals for cancer(2023) CHAVES, Henrique Koch; SILVA, Julia Maria Brandao da; SILVEIRA, Carla Cristina de Freitas da; MARQUES, Fabio Luiz Navarro; MAGALHAES, Jorge Lima deObjective: Prospect the evolution of patent applications onIdentify, extract, process data, organize and make available technological information in the form of graphical interfaces described in oncology patents containing the radioisotopes gallium-68 (68Ga), copper-64 (64Cu) and zirconium-89 (89Z) in order to understand the development of science and technology in the area.Method: The ORBIT Intelligence® platform from the company QUESTEL® was used to identify, extract, process the data, organize and make available the technological information in the form of graphical interfaces, analysis of the filed patents in force in the last 20 years in the main patent offices in the world.Result: For gallium-68, copper-64 and zirconium-89, respectively, 36, 18 and 10 families of patents containing the search terms described in the methodology were identified. In both cases, China stands out in the number of filed patent applications, depositing 61% of the total analyzed. It was also observed that many of the analyzed documents were deposited by universities, reinforcing the concept of company-university partnership. The results obtained point out that the area of this study continues to grow and the understanding of the information present in the patent documents makes itpossible to reflect on spaces to intensify the development of innovations in the oncology area.Conclusions: The results obtained demonstrate the relevance of information for the management of a country's technological development, which can serve as an efficient method to analyze, compare and monitor research and development activities in cancer and also support the planning processes organizations, as well as supporting public and private health policies.- Potential of [C-11](R)-PK11195 PET Imaging for Evaluating Tumor Inflammation: A Murine Mammary Tumor Model(2022) SOUZA, Aline Morais de; REAL, Caroline Cristiano; JUNQUEIRA, Mara de Souza; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; CHAMMAS, Roger; SAPIENZA, Marcelo Tatit; FARIA, Daniele de PaulaBackground: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [C-11](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. Methods: Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [C-11](R)-PK11195 and [F-18]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. Results: The [C-11](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [F-18]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [C-11](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. Conclusion: The [C-11](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [F-18]FDG, molecular imaging with [C-11](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.
- Patentometric analysis as a subsid to the management of technological innovation: a case study in radiopharmaceuticals for cancer(2023) CHAVES, Henrique Koch; SILVA, Julia Maria Brandao da; SILVEIRA, Carla Cristina de Freitas da; MARQUES, Fabio Luiz Navarro; MAGALHAES, Jorge Lima deObjective: Prospect the evolution of patent applications onIdentify, extract, process data, organize and make available technological information in the form of graphical interfaces described in oncology patents containing the radioisotopes gallium-68 (Ga-68), copper-64 (Cu-64) and zirconium-89 ((89)Z) in order to understand the development of science and technology in the area. Method: The ORBIT Intelligence (R) platform from the company QUESTEL (R) was used to identify, extract, process the data, organize and make available the technological information in the form of graphical interfaces, analysis of the filed patents in force in the last 20 years in the main patent offices in the world. Result: For gallium-68, copper-64 and zirconium-89, respectively, 36, 18 and 10 families of patents containing the search terms described in the methodology were identified. In both cases, China stands out in the number of filed patent applications, depositing 61% of the total analyzed. It was also observed that many of the analyzed documents were deposited by universities, reinforcing the concept of company-university partnership. The results obtained point out that the area of this study continues to grow and the understanding of the information present in the patent documents makes it possible to reflect on spaces to intensify the development of innovations in the oncology area. Conclusions: The results obtained demonstrate the relevance of information for the management of a country's technological development, which can serve as an efficient method to analyze, compare and monitor research and development activities in cancer and also support the planning processes organizations, as well as supporting public and private health policies.
- Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents(2024) MENDONCA, Fernanda Ferreira; SOBRAL, Danielle Vieira; DURANTE, Ana Claudia Ranucci; MIRANDA, Ana Claudia Camargo; MEJIA, Jorge; FARIA, Daniele de Paula; MARQUES, Fabio Luiz Navarro; BARBOZA, Marycel Figols de; FUSCALDI, Leonardo Lima; MALAVOLTA, LucianaBreast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the alpha 1, beta 1, and gamma 1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached approximately equal to 48% and approximately equal to 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized alpha 1 and beta 1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.
- [18F]FDG and [11C]PK11195 PET imaging in the evaluation of brown adipose tissue-effects of cold and pharmacological stimuli and their association with crotamine intake in a male mouse model(2023) FARIA, Daniele de Paula; CAMPEIRO, Joana D'Arc; JUNQUEIRA, Mara de Souza; REAL, Caroline Cristiano; MARQUES, Fabio Luiz Navarro; HAYASHI, Mirian Akemi Furuie; SAPIENZA, Marcelo TatitThis study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). Methods: Male C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6-9 degrees C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. Results: The cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 & PLUSMN; 1.05 vs. 2.03 & PLUSMN; 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 & PLUSMN; 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 & PLUSMN; 0.39; 21 days crotamine: 4.77 & PLUSMN; 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 & PLUSMN; 0.66 vs. 3.36 & PLUSMN; 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 & PLUSMN; 0.58, p = 0.7864) and also after CL stimulus (3.55 & PLUSMN; 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions: [11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C] PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.