Kazuhiko Tamate

Computer-controlled large scale production of high specific activity [11C]RO 15-1788 for PET studies of benzodiazepine receptors.

Ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate ([11C]RO 15-1788) has been prepared automatically with high specific activity for in vivo visualization or quantitative analysis of brain benzodiazepine receptors. The yield, radiochemical yield, radiochemical purity and specific activity of the product ready for an i.v. injection were 276 +/- 76 mCi, 50.8 +/- 7.8%, 99.3 +/- 0.3% and 2.9 +/- 0.5 Ci/mumol, respectively, taking an average of the latest 3 runs. The time required was about 25 min. Each product was sufficient to carry out three successive clinical studies by positron emission tomography (PET). All the procedures other than evaporation and filtration at the final stage were carried out with specially designed equipment connected to a central control system for radioisotope production.

Production of 3-N-[11C]methylspiperone with high specific activity and high radiochemical purity for PET studies: Suppression of its radiolysis

3-N-[11C]methylspiperone(11C-NMS, molecular weight = 409 for 12C-NMS) has been prepared automatically with high specific activity (37 +/- 18 GBq/mumol at EOS) for the measurement of dopamine D2 receptors in the human brain with a positron camera. It was observed that the radiochemical purity of 11C-NMS decreased from 97.8% (in HPLC eluate) to 83.5% (in saline, after the dispensing procedure, at 29 min from EOS), and to 79.9% in a further 59 min and that another 11C-labelled compound with a molecular weight of 425 (as a 12C-labelled compound) was formed. It was also observed that an aqueous solution of carrier methylspiperone (NMS) decomposed on 60Co irradiation and, using the same analytical conditions, gave the compound with the same retention time and the same molecular weight as 11C-NMS gave. The G-value of NMS decomposition by 60Co irradiation was estimated to be about two in an aqueous solution. The decomposition of 11C-NMS was suppressed remarkably by the addition of hydroxyl radical scavengers such as potassium iodide, and accelerated slightly by a hydrated electron scavenger such as sodium nitrate. Therefore, it was assumed that the hydroxyl radical generated by the radiolysis of water played an important role in the decomposition of 11C-NMS in the aqueous solution. Polysolvate-80 and ethyl alcohol were used as i.v. injectable additives to protect 11C-NMS against decomposition. In 47 routine productions, 2.7 +/- 1.7 GBq of 11C-NMS aqueous solutions ready for i.v. injection have been produced at 98.3 +/- 1.0% radiochemical purity using an automated synthesis apparatus. The products were used for clinical purposes with a positron camera and animal experiments.

Automatic production of 13NH3 and L-[13N]glutamate ready for intravenous injection

A system has been developed for the automatic production of 13NH3 and L-[13N]glutamate for i.v. injection. Up to 250 mCi of 13NH3 and 60 mCi of L-[13N]glutamate were produced at radiochemical purities of 99.9% with the equipment. The required times were 8.2 and 17.5 min, respectively. Pyrogen and glutamate dehydrogenase (GDH) were not detected in the product. The solution was obtained without any sterile procedure other than the filtration with an autoclaved ultrafilter (NMWL = 10,000) assembly at the final production stage. Penetration ratios through the filter were <3 × 10−6 and 2×10−7 ∼ 6×10−7 for GDH and E. Coli endotoxin, respectively. A new 47 mm diameter filter holder with a small dead volume (≈0.6 mL) was devised for easy assembly of the sterilized filter.

Remote-controlled System for a Large Scale Production of Short-lived Radioactive Substances with Cyclotron

核医学的な臨床利用に十分な量の短寿命RI (11CO, 11CO2, 13NN, 13NH3, 18F-, 62Zn2+, 123I-など) の生産が可能で, しかもそれらの生産条件の検討や迅速分析などにも利用できる短寿命RI生産システムの開発を行った。このシステムを利用することにより臨床利用の可能な数+mCiの短寿命RIを遠隔的に, しかも放射性ガス (11CO, 11CO2, 13NN) の場合は連続的に, そして放射性液体 (13NH3, 18F-など) の場合は数分の待時間で繰り返して生産することができた。一方作業者の被ばく線量はこのシステムの設置により大幅に減少した。

Simple Method for Producing 13NN and 15OO by Proton Bombardment of Aqueous Phase

A simple method has been developed for the production of 13NN and 15OO by proton irradiation of aqueous solutions. 90 mCi of 13NN was obtained in a 200 ml. of He by using 1.0M NH4CI solution at pH 11 as the target with 10 min irradiation of 15 MeV, 10 microamperemeter protons. 80 mCi/min of 15OO was continuously obtained in a 200 ml of O2 by using pure water as the target with 40 MeV, 2 microamperemeter protons. The radiochemical purity of these short-lived radioactive gases obtained by this method was greater than 99.9% by passing through a single absorber.

Fundamental Studies on Clinical Application of 13N-ammonia

放医研の医療用サイクロトロンを利用して, 13N-アンモニアを製造し, これの家兎の腸管内および静注の2つの投与経路での肝および心の13N-放射能動態の観察を行った。これに基づき, アンモニア代謝モデルを設定し, その解を適当な近似式に変換し, これにより腸管からのアンモニア吸収能, 肝内門脈分布, 実質細胞分布などで規定される諸パラメータ抽出の理論を展開した。