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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.

6-[18F]Fluoro-L-dopa (L-3,4-dihydroxy-6-[18F]fluorophenylalanine; 6-[18F]FDPA) is useful to assess presynaptic dopamine metabolism in central nervous system. In this paper, we report on the usefulness of the 6-[18F]FDOPA synthesis system developed for the routine synthesis. This system consists of the 6-[18F]FOPA synthesis and the separation units in conjunction with controller using a personal computer. The synthesis time of 6-[18F]FDOPA was 73 minutes. The typical yield and specific activity were 1.4-2.4 GBq and 244-270 MBq/mumol at the end of synthesis, respectively, under the irradiation condition of 50 microA for 130 minutes. The radiochemical yields of 6-[18F]FDOPA were 31.3-38.7% based on the [18F]acetylhypofluorite, and the results were affected with the condition of potassium acetate (AcOK) to produce gaseous [18F]acetylhypofluorite. This system is useful for the routine production of 6-[18F]FDOPA because of its high yield and high specific activity while maintaining AcOK in good condition, and decreasing the radiation exposure for chemist.

We measured regional distribution of the muscarinic cholinergic receptor in the normal human brain with 11C-benztropine (BZT) and positron emission tomography (PET) using an anatomical standardization technique. Seven normal volunteers who gave informed consents were involved in this study. Immediately after intravenous injection of 11C-BZT into the subjects, we started dynamic PET scanning and serial frequent arterial blood sampling. Analyses of plasma metabolites were also performed at selected time points and plasma time activity curves (TAC) of unmetabolized ligand were generated. From these PET and TAC data, we obtained Patlak plot slope calculation images. Using the HBA (human brain atlas) system, the Patlak plot slope calculation image of each subject was transformed into the shape of the standard brain. Mean and standard deviation (SD) calculation images were generated from those anatomically standardized images. On these mean and SD images, we placed regions of interest which were previously outlined on a MR image of the standard brain. From those data, we found the highest receptor distribution in the striatum and occipital cortex, as well as high distribution in the frontal, parietal, and temporal cortices, which were consistent with previous reports. These results suggested that anatomical standardization of PET receptor images with 11C-BZT will be useful for delineating the physiological or pathological alterations of the muscarinic cholinergic receptor in the human brain.

A [15O]water production and infusion system was newly developed for blood flow study with positron emission tomography. The system utilizes a electrostatic cooling unit to liquify [15O]vapor in a coiled plastic tube. Labeled [15O]water is collected into an infusion syringe by a wash of the trapping tube with saline. The system is simple and efficient; the recovery rate of [15O]water is over 90% at 10 degrees C of cooling temperature.

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

18F-fluorodeoxygalactose (18FDGal) is a tracer for the evaluation of galactose metabolism in the tissue. PET with 18FDGal was performed in a hepatoma (HCC) patient with lumbar bone metastasis. The image at 45 min after i.v. injection of 18FDGal demonstrated very high uptake by the bone metastasis with tumor-to-surrounding normal tissue ratio of 36. The tumor uptake expressed by differential absorption ratio was much higher than that in the cirrhotic liver and kidney. The result indicated that the HCC maintained high activity of galactose metabolism and rises the potential of this tracer for detecting extrahepatic metastases of HCC using PET.

To demonstrate the distribution of 2-deoxy-2-18F-fluoro-D-glucose (FDG) within the tumor in vivo, C3H/He mice transplanted with FM3A tumors were studied one hour after intravenous injection of FDG using whole-body, macro- and micro-autoradiography. The whole-body autoradiograph showed that the tumor mass as well as the brain, heart, bone marrows, and the diaphragm and crus diaphragm were clearly visualized. The macro-autoradiograph showed the heterogeneous distribution of FDG in the tumor mass. Markedly dense areas surrounding the tumor and the necrotic area were observed. Micro-autoradiograph showed the high grain densities in the macrophages between the necrosis and viable tumor cells, and in the young granulation tissues demarcating between the tumor and surrounding intact host tissues. Our results showed that the FDG uptake in the tumors may reflect not only the uptake by the tumor cells but also that by the inflammatory reaction elements.