n-n-dimethyl-n-(18f)fluoromethyl-2-hydroxyethylammonium and Disease-Models--Animal

Diabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.. Low-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100) and LDLR(-/-)ApoB(100/100)) were studied. Distribution kinetics of choline analogue (18)F-fluoromethylcholine ((18)F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of (18)F-FMCH and glucose analogue (18)F-fluorodeoxyglucose ((18)F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The (18)F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers.. The aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of (18)F-FMCH was rapid. Both the absolute (18)F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest (18)F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. (18)F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with (18)F-FDG, (18)F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice.. Type 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer (18)F-FMCH is a potential tool to study vascular inflammation associated with diabetes.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Biomarkers; Choline; Cytokines; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Models, Animal; Fluorine Radioisotopes; Hypercholesterolemia; Macrophages; Mice, Inbred C57BL; Mice, Transgenic; Plaque, Atherosclerotic; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Tissue Distribution

Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.. Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed.. The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN.. Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

Topics: Animals; Brain; Cell Line, Tumor; Choline; Diagnosis, Differential; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Humans; Kinetics; Necrosis; Neoplasm Grading; Positron-Emission Tomography; Radiation Injuries; Radiopharmaceuticals; Rats, Inbred F344; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Abdominal aortic aneurysm (AAA) is a frequent form of atherothrombotic disease, whose natural history is to enlarge and rupture. Indicators other than AAA diameter would be useful for preventive surgery decision-making, including positron-emission tomography (PET) methods permitting visualization of aortic wall leukocyte activation relevant to prognostic AAA evaluation. In this study, we compare three PET tracers of activated leukocytes, 18F-fluoro-deoxy-glucose (FDG), 18F-fluoro-methyl-choline (FCH), and 18F-DPA714 (a peripheral benzodiazepine receptor antagonist) for in vivo PET quantification of aortic wall inflammation in rat experimental AAAs, in correlation with histopathological studies of lesions.. AAAs were induced by orthotopic implantation of decellularized guinea pig abdominal aorta in 46 Lewis rats. FDG-PET (n = 20), FCH-PET (n = 8), or both (n = 12) were performed 2 weeks to 4 months after the graft, 1 hour after tracer injection (30 MBq). Six rats (one of which had FDG-PET) underwent 18F-DPA714-PET. Rats were sacrificed after imaging; AAAs and normal thoracic aortas were cut into axial sections for quantitative autoradiography and histologic studies, including ED1 (macrophages) and CD8 T lymphocyte immunostaining. Ex vivo staining of AAAs and thoracic aortas with 18F-DPA714 and unlabeled competitors was performed.. AAAs developed in 35 out of 46 cases. FCH uptake in AAAs was lower than that of FDG in all cases on imaging, with lower AAA-to-background maximal standardized uptake value (SUV(max)) ratios (1.78 ± 0.40 vs 2.71 ± 0.54; P < .01 for SUV(max) ratios), and lower AAA-to-normal aorta activity ratios on autoradiography (3.52 ± 1.26 vs 8.55 ± 4.23; P < .005). FDG AAA-to-background SUV(max) ratios correlated with the intensity of CD8 + ED1 staining (r = .76; P < .03). FCH AAA-to-background SUV(max) ratios correlated with the intensity of ED1 staining (r = .80; P < .03). 18F-DPA714 uptake was similar in AAAs and in normal aortas, both in vivo and ex vivo.. In rat experimental AAA, characterized by an important aortic wall leukocytes activity, FDG-PET showed higher sensitivity than FCH-PET and 18F-DPA714-PET to detect activated leukocytes. This enhances potential interest of this tracer for prognostic evaluation of AAA in patients.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Autoradiography; Chemotaxis, Leukocyte; Choline; Disease Models, Animal; Fluorodeoxyglucose F18; Guinea Pigs; Leukocytes; Positron-Emission Tomography; Predictive Value of Tests; Pyrazoles; Pyrimidines; Radiopharmaceuticals; Rats; Rats, Inbred Lew; Sensitivity and Specificity; Transplantation, Heterologous

To compare choline concentration/amount at proton magnetic resonance spectroscopy (H-MRS) and [18F]-fluoromethylcholine (FCH) uptake at positron emission tomography (PET) in a tumour animal model.. Twenty-two rats bearing grafted syngenic rhabdomyosarcoma in both thighs were examined on a 3T MR system and on a small animal PET system. Total choline concentration was measured on proton MR spectra using a so-called 'best internal fitting' volume of interest. Choline uptake was expressed as mean and maximum standardized uptake value (SUV and SUVmax, respectively) and as the percent of injected dose (%ID) after tumour delineation on fused PET-MR images. Data sets were displayed on standard scatter plots.. Thirty-six tumours were available for analysis. The area under the curve of the 3.2 ppm choline peak ranged from 69 to 476 (mean, 192) in arbitrary units. Mean SUV values ranged from 0.05 to 0.49 (mean, 0.19) and the %ID from 0.05 to 2.28 (mean, 0.54). Scatter plots failed to reveal quantitative relationship between choline concentration and uptake. Empirically data-driven cut-off lines applied to choline amount (choline concentration x tumour volume) versus choline uptake suggested a paradoxically negative relationship.. Total choline concentration did not correlate with FCH uptake in a tumour experimental model. A negative feedback of high values of total choline amount on cellular FCH uptake seemed to be present.

Topics: Animals; Choline; Disease Models, Animal; Fluorine Radioisotopes; Magnetic Resonance Spectroscopy; Positron-Emission Tomography; Rats; Rhabdomyosarcoma

To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in (18)F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model.. Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT. Total choline concentration was expressed in arbitrary units as the area under the curve of the 3.2-ppm peak on H-MR spectra. FCH uptake was expressed as maximum standardized uptake value (SUV(max)) and as the % of injected dose per gram (%ID/g) after precise tumour delineation on hybrid PET-MR images. Pre- and post-RT data were compared using the Student's paired t test, and results were expressed as mean+/-S.D.. Seventeen tumours were available for analysis. A mean drop in choline concentration of 45% was observed 3 days after irradiation (P<.001), whereas a concomitant mean increase in SUV(max) of 41% was observed (P=.006). Choline concentration reincreased on later time points.. Opposite trend between increased FCH uptake and decreased tCho peak was observed at 3 days. Later (9 and 16 days), uptake remained stable and tCho peak reincreased.

Topics: Alginates; Animals; Biological Transport; Choline; Disease Models, Animal; Glucuronic Acid; Hexuronic Acids; Magnetic Resonance Spectroscopy; Male; Positron-Emission Tomography; Protons; Rats; Rhabdomyosarcoma; Survival Rate; Time Factors; Treatment Outcome