MILENA SALES PITOMBEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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- 11C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls: a cross-sectional study(2021) SOUZA, Aline Morais de; PITOMBEIRA, Milena Sales; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; REAL, Caroline Cristiano; FARIA, Daniele de Paula11C-PK11195 is a positron emitter tracer used for Positron Emission Tomography (PET) imaging of innate immune cell activation in studies of neuroinflammatory diseases. For the image quantitative analysis, it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition (plasma intact fraction). Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition. The purpose of this study is to compare 11C-PK11195 plasma metabolization rate between healthy controls and multiple sclerosis (MS) patients and evaluate the interference of sex, age, treatment, and disease phenotype in the tracer intact fraction measured in arterial plasma samples. 11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients (n = 50) and healthy controls (n = 23) at 20, 45, and 60 minutes after 11C-PK11195 injection. Analyses were also stratified by sex, age, treatment type, and MS phenotype. The results showed no significant differences in the metabolization rate of healthy controls and MS patients, or in the stratified samples. In conclusion, 11C-PK11195 metabolization has the same rate in patients with MS and healthy controls, which is not affected by sex, age, treatment, and disease phenotype. Thus, these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition, by using a population metabolization rate average. The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School (approval No. 624.065) on April 23, 2014.
- Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study(2022) PITOMBEIRA, Milena Sales; KOOLE, Michel; CAMPANHOLO, Kenia R.; SOUZA, Aline M.; DURAN, Fabio L. S.; SOLLA, Davi J. Fontoura; MENDES, Maria F.; PEREIRA, Samira L. Apostolos; RIMKUS, Carolina M.; BUSATTO, Geraldo Filho; CALLEGARO, Dagoberto; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaPurpose Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. Methods We used the 18-kDa translocator protein (TSPO) tracer (R)[C-11]PK11195 and [C-11]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)[C-11]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [C-11]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). Results In the VOI-based analysis, [C-11]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[C-11]PK11195 V-T were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[C-11]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [C-11]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[C-11]PK11195 V-T and lower [C-11]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T-2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [C-11]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[C-11]PK11195 V-T (P = 0.013). Conclusions Widespread innate immune cells profile and marked loss of myelin in T-2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.
- Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study(2022) CAMPANHOLO, K. R.; PITOMBEIRA, M. S.; RIMKUS, C. M.; MENDES, M. F.; APOSTOLOS-PEREIRA, S. L.; BUSATTO FILHO, G.; CALLEGARO, D.; BUCHPIGUEL, C. A.; DURAN, F. L. S.; FARIA, D. De PaulaBackground: Cognitive impairment is one of the concerns of Multiple Sclerosis (MS) and has been related to myelin loss. Different neuroimaging methods have been used to quantify myelin and relate it to cognitive dysfunctions, among them Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI), and, more recently, Positron Emission Tomography (PET) with C-11-PIB. Objective: To investigate different myelin imaging modalities as predictors of cognitive dysfunction. Methods: Fifty-one MS patients and 24 healthy controls underwent clinical and neuropsychological assessment and MTR, DTI (Axial Diffusion-AD and Fractional Anisotropy-FA maps), and C-11-PIB PET images in a PET/MR hybrid system. Results: MTR and DTI(FA) differed in patients with or without cognitive impairment. There was an association of DTI(FA) and DTI(AD) with cognition and psychomotor speed for progressive MS, and of C-11-PIB uptake and MTR for relapsing-remitting MS. MTR in the Thalamus (beta=-0.51, p=0.021) and Corpus Callosum (beta=-0.24, p=0.033) were predictive of cognitive impairment. DTI-FA in the Caudate (beta=-26.93, p=0.006) presented abnormal predictive result. Conclusion: Lower myelin content by C-11-PIB uptake was associated with worse cognitive status. MTR was predictive of cognitive impairment in MS.
- Evaluation of Non-Invasive Methods for (R)-[11C]PK11195 PET Image Quantification in Multiple Sclerosis(2024) MANTOVANI, Dimitri B. A.; PITOMBEIRA, Milena S.; SCHUCK, Phelipi N.; ARAUJO, Adriel S. de; BUCHPIGUEL, Carlos Alberto; FARIA, Daniele de Paula; SILVA, Ana Maria M. daThis study aims to evaluate non-invasive PET quantification methods for (R)-[C-11]PK11195 uptake measurement in multiple sclerosis (MS) patients and healthy controls (HC) in comparison with arterial input function (AIF) using dynamic (R)-[C-11]PK11195 PET and magnetic resonance images. The total volume of distribution (VT) and distribution volume ratio (DVR) were measured in the gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, cerebellum, and brainstem using AIF, the image-derived input function (IDIF) from the carotid arteries, and pseudo-reference regions from supervised clustering analysis (SVCA). Uptake differences between MS and HC groups were tested using statistical tests adjusted for age and sex, and correlations between the results from the different quantification methods were also analyzed. Significant DVR differences were observed in the gray matter, white matter, putamen, pallidum, thalamus, and brainstem of MS patients when compared to the HC group. Also, strong correlations were found in DVR values between non-invasive methods and AIF (0.928 for IDIF and 0.975 for SVCA, p < 0.0001). On the other hand, (R)-[C-11]PK11195 uptake could not be differentiated between MS patients and HC using VT values, and a weak correlation (0.356, p < 0.0001) was found between VTAIF and VTIDIF. Our study shows that the best alternative for AIF is using SVCA for reference region modeling, in addition to a cautious and appropriate methodology.