RODRIGO BARBOSA DE AGUIAR
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- A quantitative sequencing based method for the monitoring of clonal expansion(2012) STRAUSS, Bryan E.; ZANATTA, Daniela; AGUIAR, Rodrigo B. de
- Technetium glucose complexes as potential cancer imaging agents(2015) DAPUETO, Rosina; AGUIAR, Rodrigo B.; MORENO, Maria; MACHADO, Camila M. L.; MARQUES, Fabio L. N.; GAMBINI, Juan P.; CHAMMAS, Roger; CABRAL, Pablo; PORCAL, WilliamsGLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue (F-18-FDG) with PET images, worldwide. New glucose analogs radiolabeled with Tc-99m could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. D-Glucose (Tc-99m-IDAG) and 2-D-deoxyglucose (Tc-99m-AADG) organometallic complexes were proposed and studied as potential F-18-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with Tc-99m. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with F-18-FDG in order to compare the uptake of Tc-99m-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (TcO4)-Tc-99m to obtain the Tc-99m-IDAG and Tc-99m-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, Tc-99m-IDAG and Tc-99m-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 +/- 3.73 and 2.88 +/- 1.40 for Tc-99m-IDAG and Tc-99m-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of Tc-99m-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging.
- [(99)mTc(CO)(3)]- Radiolabeled Bevacizumab: In vitro and in vivo Evaluation in a Melanoma Model(2013) CAMACHO, Ximena; GARCIA, Maria Fernanda; CALZADA, Victoria; FERNANDEZ, Marcelo; CHABALGOITY, Jose A.; MORENO, Maria; AGUIAR, Rodrigo Barbosa de; ALONSO, Omar; GAMBINI, Juan Pablo; CHAMMAS, Roger; CABRAL, PabloIntroduction: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies. Objective: To radiolabel bevacizumab with [Tc-99m(CO)(3)(OH2)(3)]+ and evaluate it in vivo and in vitro for melanoma imaging properties. Methods: Bevacizumab was radiolabeled with [Tc-99m(CO)(3)(OH2)(3)]+ ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays. Results: We demonstrate that Tc-99m(CO)(3) -bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of Tc-99m(CO)(3)-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of Tc-99m(CO)(3)-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. Conclusions: Tc-99m(CO)(3)-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy.
conferenceObject Sequencing of a Genetic Barcode Reveals Altered Population Dynamics in a Mouse Model of Transplanted Hematopoietic Stem Cells Transduced with a Lentivirus Encoding LMO2(2013) STRAUSS, Bryan E.; ZANATTA, Daniela B.; AGUIAR, Rodrigo; TSUJITA, Maristela; BORELLI, Primavera- Genetic barcode sequencing for screening altered population dynamics of hematopoietic stem cells transduced with lentivirus(2014) ZANATTA, Daniela B.; TSUJITA, Maristela; BORELLI, Primavera; AGUIAR, Rodrigo B.; FERRARI, Daniel G.; STRAUSS, Bryan E.Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic changes in clonality of lentivirus transduced cells upon Sanger sequence analysis of a specially designed genetic barcode. In our approach, changes in the electropherogram peaks are measured and compared between successive time points, revealing alteration in the cell population. After in vitro validation, barcoded lentiviral libraries carrying IL2RG or LMO2 transgenes, or empty vector were used to transduce mouse hematopoietic (ckit+) stem cells, which were subsequently transplanted in recipient mice. We found that neither the empty nor IL2RG encoding vector had an effect on cell dynamics. In sharp contrast, the LMO2 oncogene was associated with altered cell dynamics even though hematologic counts remained unchanged, suggesting that the barcode could reveal changes in cell populations not observed by the frontline clinical assay. We describe a simple and sensitive method for the analysis of clonality, which could be easily used by any laboratory for the assessment of cellular behavior upon lentiviral transduction.
- Blocking FGF2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings(2016) AGUIAR, Rodrigo Barbosa de; PARISE, Carolina Bellini; SOUZA, Carolina Rosal Teixeira; BRAGGION, Camila; QUINTILIO, Wagner; MORO, Ana Maria; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; CHAMMAS, Roger; MORAES, Jane Zveiter deCompelling evidence suggests that fibroblast growth factor 2 (FGF2), overexpressed in melanomas, plays an important role in tumor growth, angiogenesis and metastasis. In this study, we evaluated the therapeutic use of a new anti-FGF2 monoclonal antibody (mAb), 3F12E7, using for that the B16-F10 melanoma model. The FGF2 neutralizing effect of this antibody was certified by in vitro assays, which allowed the further track of its possible in vivo application. 3F12E7 mAb could be retained in B16-F10 tumors, as shown by antibody low-pH elution and nuclear medicine studies, and also led to reduction in number and size of metastatic foci in lungs, when treatment starts one day after intravenous injection of B16-F10 cells. Such data were accompanied by decreased CD34(+) tumor vascular density and impaired subcutaneous tumor outgrowth. Treatments starting one week after melanoma cell intravenous injection did not reduce tumor burden, remaining the therapeutic effectiveness restricted to early-adopted regimens. Altogether, the presented anti-FGF2 3F12E7 mAb stands as a promising agent to treat metastatic melanoma tumors in adjuvant settings.
- Biological evaluation of two glucose derivatives radiolabeled with Tc-99m as potential cancer imaging agents(2014) DAPUETO, Rosina; FERNANDEZ, Marcelo; AGUIAR, Rodrigo; MORENO, Maria; MACHADO, Camila; MARQUES, Fabio; GAMBINI, Juan P.; CHAMMAS, Roger; CABRAL, Pablo; PORCAL, Williams