RESUMO
BACKGROUND: 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 [11C](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 [11C](R)-PK11195 and [18F]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. RESULTS: The [11C](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [18F]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 [11C](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. CONCLUSION: The [11C](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 [18F]FDG, molecular imaging with [11C](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.
RESUMO
11C-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.
