ABSTRACT
Phosphoinositide turnover is closely connected to modulation of synaptic function and is part of an important second messenger-producing system. New radioligands for imaging second messenger systems by positron emission tomography have been developed: carbon-11-labeled 1,2-diacylglycerols. The theoretical background of second messenger imaging is described in detail and the relation between the biologically active compounds and potential tracers for imaging second messenger systems is discussed. We report informative findings on postsynaptic biological responses in the living human brain of healthy normal subjects and with various diseases.
Subject(s)
Brain/metabolism , Second Messenger Systems/physiology , Tomography, Emission-Computed/methods , Adult , Animals , Carbon Radioisotopes , Diglycerides/chemistry , Diglycerides/pharmacokinetics , Humans , Male , Parkinson Disease/metabolism , Phosphatidylinositols/metabolism , Radioactive Tracers , Rats , Rats, Wistar , Reference Values , Tomography, Emission-Computed/standardsABSTRACT
Positron emission tomography (PET) radiotracers have very short physical half-lives. It is hard to complete a bacterial endotoxins test prior to release from medical institutes. For endotoxin quantitative determination, limulus amebocyte lysate (LAL) reagent and kinetic-turbidimetry system were previously developed. We investigated the possibility of a short time test by means of positively charged filters. As a result of this study, the effects of positively charged filters on endotoin removal were over 99.5% for [18F]FDG and [18F]NaF, which were contaminated with the indicated concentration of endotoxin. Combining this filter and the kinetic-turbidimetric method, it was possible to complete a bacterial endotoxins test in 5 min prior to the patient's administration. This test should be required prior to release for PET radiopharmaceutical quality control. It has been suggested that this combination is a good method for this purpose.
Subject(s)
Drug Contamination/prevention & control , Endotoxins/isolation & purification , Micropore Filters , Radiopharmaceuticals , Tomography, Emission-Computed , Endotoxins/analysis , Fluorodeoxyglucose F18 , Hydrogen-Ion Concentration , Nephelometry and Turbidimetry , Quality Control , Sodium FluorideABSTRACT
We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10 weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.
