CAROLINE CRISTIANO REAL GREGORIO
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- 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.
- [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.
- Sex-specific regulation of miR-22 and ERα in white adipose tissue of obese dam's female offspring impairs the early postnatal development of functional beige adipocytes in mice(2024) MENDONCA, Mariana de; BOLIN, Anaysa Paola; OLIVEIRA, Nayara Preste de; REAL, Caroline Cristiano; HU, Xiaoyun; HUANG, Zhan-Peng; WANG, Da-Zhi; RODRIGUES, Alice CristinaDuring inguinal adipose tissue (iWAT) ontogenesis, beige adipocytes spontaneously appear between postnatal 10 (P10) and P20 and their ablation impairs iWAT browning capacity in adulthood. Since maternal obesity has deleterious effects on offspring iWAT function, we aimed to investigate its effect in spontaneous iWAT browning in offspring. Female C57BL/6 J mice were fed a control or obesogenic diet six weeks before mating. Male and female offspring were euthanized at P10 and P20 or weaned at P21 and fed chow diet until P60. At P50, mice were treated with saline or CL316,243, a beta 3-adrenoceptor agonist, for ten days. Maternal obesity induced insulin resistance at P60, and CL316,243 treatment effectively restored insulin sensitivity in male but not female offspring. This discrepancy occurred due to female offspring severe browning impairment. During development, the spontaneous iWAT browning and sympathetic nerve branching at P20 were severely impaired in female obese dam's offspring but occurred normally in males. Additionally, maternal obesity increased miR-22 expression in the iWAT of male and female offspring during development. ER alpha, a target and regulator of miR22, was concomitantly upregulated in the male's iWAT. Next, we evaluated miR-22 knockout (KO) offspring at P10 and P20. The miR-22 deficiency does not affect spontaneous iWAT browning in females and, surprisingly, anticipates iWAT browning in males. In conclusion, maternal obesity impairs functional iWAT development in the offspring in a sex-specific way that seems to be driven by miR-22 levels and ER alpha signaling. This impacts adult browning capacity and glucose homeostasis, especially in female offspring.