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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 217 records · Page 12Linked to original sources

Studies on 18F-labeled pyrimidines. II. Metabolic investigation of 18F-5-fluorouracil, 18F-5-fluoro-2'-deoxyuridine and 18F-5-fluorouridine in rats.

18F-labeled 5-fluorouracil(FUra), 5-fluoro-2'-deoxyuridine(FdUrd), and 5-fluorouridine ( FUrd ) were synthesized with high radiochemical purities. The 18F-labeled pyrimidines were injected into rats. The metabolites in serum, bile, and urine were analyzed up to 2 h after administration by radio-high performance liquid chromatography (HPLC). The blood clearance of three pyrimidines was very rapid. In the serum the nucleosides and base disappeared very rapidly with a biological half-life of about 2 min and most of them had disappeared by 60 min. The metabolites in the urine were similar to those in the serum. In the bile pyrimidine nucleosides and base were not detected. 18F- was found in the metabolites. Our results explain the high uptakes in the kidney and liver in biodistribution studies of the 18F-labeled pyrimidines.

Animals↗

Syntheses of 18F-labeled pyrimidines and their usefulness for tumor imaging.

18F-Labeled 5-fluorouracil(FUra), 5-fluoro-2'-deoxyuridine(FdUrd) and 5-fluorouridine(FUrd) were synthesized with high radiochemical purities. Biodistribution of the 18F-pyrimidines in tumor-bearing rats, mice or a rabbit was examined. Blood clearance of the 18F-pyrimidines was very rapid. The kidney and liver showed the high uptake and rapid clearance which was due to the metabolism and excretion. The 18F-concentration in the tumor was due to the metabolism and excretion. The 18F-concentration in the tumor was also high and clearance was very slow compared with those in other organs. Tumor uptakes of 18F-FdUrd were also shown by positron emission tomography and autoradiography. Biodistributions of the 18F-FdUrd and radio-deoxythymidine(dThd) were different between several organs, but similar distribution patterns in the tumor were observed by autoradiography.

Animals↗

[Automated synthesis system for production of 11C-glucose].

A fully automated synthesis system of 11C-glucose by the photosynthesis method has been developed for clinical use. This system has been designed to be as convenient as possible for routine use, and the full automation of the whole procedure from the target gas recovery to collection of the final 11C-glucose/fructose mixture has been accomplished by microcomputer control. A mixture of 11C-glucose/fructose (1:1) was obtained with 20 approximately 35% of radiochemical yield within 60 min.

Carbon Dioxide↗

Studies on 18F-labeled pyrimidines. Tumor uptakes of 18F-5-fluorouracil, 18F-5-fluorouridine, and 18F-5-fluorodeoxyuridine in animals.

Three 18F-labeled pyrimidines, 18F-5-fluorouridine (18F-5-FUR), 18F-5-fluorouracil (18F-5-FU), and 18F-5-fluorodeoxyuridine (18F-5-FdUR), were examined regarding tissue distribution and tumor uptake in ascitic hepatoma AH109A-bearing rats. The differential absorption ratios of tumors of 18F-5-FUR, 18F-5-FU, and 18F-5-FdUR were 0.75 +/- 0.21, 0.92 +/- 0.15, and 0.96 +/- 0.24 at 30 min, and 0.37 +/- 0.09, 0.64 +/- 0.34, and 0.60 +/- 0.17 at 120 min, respectively. The tumor-to-organ ratios obtained with three radiopharmaceuticals, especially with blood, heart, lung, muscle, and brain were high and these ratios increased with time. The tumor-to-organ ratios obtained with 18F-5-FdUR were always 1.3-4 times higher than 18F-5-FU and 18F-5-FUR. We concluded that 18F-5-FdUR was a suitable radiopharmaceutical for tumor imaging. Positron emission tomography of a rabbit tumor located on the chest with 18F-5-FdUR clearly showed the tumor within 1 h.

Animals↗

[Whole body autoradiography by positron emitting radionuclides].

The technique of freezing whole body autoradiography using positron emitting nuclides has been developed in the present study. Because of rapid decay of positron emitters, a frozen section to contact with a X-ray film must be prepared within a few hours. All the procedures to obtain autoradiograms of rats using 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) or 11C-glucose-fructose mixture (11C-glucose) were described in detail. In the present technique, exposure must be performed at -20 degrees C to keep a section frozen. Density of X-ray films after exposure at 20 degrees C or -20 degrees C was examined using various radioactive sections. The reduction of the density exposed at -20 degrees C was observed. But the density exposed at -20 degrees C was proportional to the radioactivity. Freezing whole body autoradiography of rats bearing subcutaneous AH109A tumors was performed using 18F-FDG (half life of 109.7 min) and 11C-glucose (half life of 20 min). Density of tumors and other organs on the autoradiogram was comparable with tissue distribution studies of 18F-FDG and 11C-glucose. Freezing whole body autoradiography can be feasible for the analysis of tissue distribution on positron emitting radiopharmaceuticals.

Animals↗

Experimental study for cancer diagnosis with positron-labeled fluorinated glucose analogs: [18F]-2-fluoro-2-deoxy-D-mannose: a new tracer for cancer detection.

18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65 +/- 0.61% dose 18 dose F-FDG/g and 2.65 +/- 0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance both 18F-FDG and 18F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas. Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM, which is a by-product of 18F-FDG synthesis was also an excellent cancer diagnostic agent as well as 18F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET.

Animals↗

Synthesis of 18F-6-fluoropurine and 18F-6-fluoro-9-beta-d-ribofuranosylpurine.

Introduction of fluorine-18 into the 6-position of purines is described. 18F-6-fluoropurine and 18F-6-fluoro-9-beta-D-ribofuranosylpurine were prepared with high radiochemical yields by nucleophilic displacement of the trimethylammonio-group of purine with 18F-fluoride under mild conditions. 18F-labeling conditions such as reaction temperature and time, addition of crown ether and dose of a substrate have been studied. Under adequate conditions, yields of about 38% in the case of free base and about 63% in the case of ribofuranosyl derivative have been obtained. The latter compound has also been prepared in a non-carrier-added state. The stability of 18F-purines was examined in Tris buffer at 37 degrees.

Fluorouracil↗

Preparation of 18F-labeled 6- and 2-fluoro-9-benzylpurine as a potential brain-scanning agent.

The preparations of [18F]-6-fluoro-9-benzylpurine(I) and [18F]-2-fluoro-9-benzylpurine(II) are described. (I) was prepared by two methods: (i) halogen exchange of 6-chloro-9-benzylpurine with Ag 18F; and (ii) displacement of trimethylpurin-6-ylammonium chloride with K 18F, followed by 9N benzylation. The latter labeling method was far superior to the former, both in radiochemical yield and in specific activity. (I) was relatively stable in a Tris-HCl buffer (0.4 M, pH 7.6) at 37 degrees C, but was easily hydrolyzed in 1 N HCl. Biodistribution of (I) in mice demonstrated high uptake in the brain. (I) can be expected to be a potential brain-scanning radiopharmaceutical for positron computed tomography.

Animals↗

Aspects of the preparation of 18F-2-deoxy-2-fluoro-D-glucose (18FDG) for medical use.

Fluorine-18-2-deoxy-2-fluoro-D-glucose (18FDG) for medical use had been prepared with the attention regarding radiochemical yield and purity, specific activity and quality control. More than four 18F-by-products in 18F-adducts from the reaction of triacetyl glucal with 18F2 were detected by the autoradiography of thin layer plates in which two by-products could not be perfectly removed by a column chromatography, and selective collection of the eluate gave 18FDG with the purity of 96.7% as an average in 12 runs. At end of synthesis (EOS) 259-925 MB (7-25 mCi) of a sterilized, isotonic solution of 18FDG was obtained with the specific activity of 629-851 MBq (17-23 mCi)/mg at end of bombardment (EOB) after preparation time of 3-3.5 hr, in which bacteria and pyrogen were not detected.

Chromatography↗

Convenient 77Kr production method for medical use.

A convenient method of 77Kr production has been developed for its routine medical use in cerebral blood flow measurement. An aqueous solution of NaBr (40 wt%) was used as the target and 77Kr produced by the 79Br(p, 3n)77Kr reaction was rapidly recovered from the target under a He stream. The optimal target thickness was determined to be 5 approximately 6 mm by investigating radionuclidic purity and proton current effect on the yield. About 740 MBq (20 mCi) of 77Kr with a radionuclidic purity of 92% was obtained within 5 min after a 5 microA-20 min irradiation. The present method has been demonstrated to be suitable for routine 77Kr production.

Cerebrovascular Circulation↗