MARA DE SOUZA JUNQUEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
conferenceObject Radioactive and near-infrared fluorescence in vivo imaging of Non-Hodgkin Lymphoma using 99mTc/Cy7-Fab(Bevacizumab)(2021) CAMACHO, X.; PERRONI, C.; CARNEIRO, C.; JUNQUEIRA, M.; FARIA, D.; GARCIA, M.; FERNANDEZ, M.; BUCHPIGUEL, C.; CERECETTO, H.; CHAMMAS, R.; RIVA, E.; CABRAL, P.; GAMBINI, J.- Radio- and Fluorescent-Labeling of Rituximab Based on the Inverse Electron Demand Diels-Alder Reaction(2021) GARCIA, Maria Fernanda; JUNQUEIRA, Mara de Souza; MORORO, Janio da Silva; CAMACHO, Ximena; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GALLAZZI, Fabio; CHAMMAS, Roger; QUINN, Thomas; CABRAL, Pablo; CERECETTO, HugoThe bioorthogonal reaction between([1,2,4,5])tetrazines with trans-cyclooctene through the inverse electron demand Diels-Alder (IEDDA) has been described as powerful bioconjugation tool. In this work, we explore the IEDDA as a modular conjugation strategy for in vitro and in vivo labeling of Rituximab for the generation of radioactive and fluorescently label immunoconjugates. The strategy allowed the generation, in vitro and in vivo, of conjugated Rituximab with cyanine 5 and 7 and the gamma emmiter technetium-99m.
- 99mTechnetium-or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents(2021) CAMACHO, Ximena; PERRONI, Carolina; MACHADO, Camila L.; CARNEIRO, Camila de Godoi; JUNQUEIRA, Mara de Souza; FARIA, Daniele; GARCIA, Maria F.; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; BUCHPIGUEL, Carlos A.; CERECETTO, Hugo; CHAMMAS, Roger; RIVA, Eloisa; CABRAL, Pablo; GAMBINI, Juan P.Background: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. Objective: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37 degrees C, derivatized with NHS-HYNIC-Tfa and radiolabeled with Tc-99m. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with Tc-99m via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
- [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.
- Synthesis of hydrophilic HYNIC-[1,2,4,5]tetrazine conjugates and their use in antibody pretargeting with Tc-99m(2018) GARCIA, Maria Fernanda; GALLAZZI, Fabio; JUNQUEIRA, Mara de Souza; FERNANDEZ, Marcelo; CAMACHO, Ximena; MORORO, Janio da Silva; FARIA, Daniele; CARNEIRO, Camila de Godoi; COUTO, Marcos; CARRION, Federico; PRITSCH, Otto; CHAMMAS, Roger; QUINN, Thomas; CABRAL, Pablo; CERECETTO, HugoPretargeted imaging, based on the highly reactive process between [1,2,4,5]tetrazines with trans-cyclooctene (TCO), appears as an attractive strategy to overcome disadvantages associated with traditional radioimmunoconjugates. To be successful, the radiolabeled component should react in vivo with the conjugated antibody and the non reactive excess clear fast from the organism. Herein, we explore the in vivo effects of hydrophilic linker incorporation into [1,2,4,5]tetrazine systems bearing a 6-hydrazinonicotinyl (HYNIC) moiety for technetium-99m coordination. Incorporation of a polypeptide chain containing hydrophilic aminoacids, resulted in a derivative with renal clearance. Pretargeted bevacizumab imaging was used as proof of concept.