Katsuyuki Minegishi

Fully automated production of iodine-124 using a vertical beam.

A fully automated system for the production of iodine-124, based on techniques of vertical-beam irradiation and dry distillation, was developed. The system, coupled with a capsulated target, was able to irradiate the (124)TeO(2) target up to 29 μA for 1-4h, which yielded iodine-124 with an almost constant yield of 6.9 MBq/μAh at the end of bombardment. All procedures were performed automatically and repeatedly. The newly developed system would be suitable for routine, large-scale productions of iodine-124.

Efficient system for the preparation of [13N]labeled nitrosamines

In the present Letter, a fast and reproducible method for the synthesis of N-[(13)N]nitrosamines is reported. The labeling strategy is based on trapping [(13)N]NO2- in an anion exchange resin. The reaction with secondary amines in the presence of Ph(3)P and Br(2) led to the formation of the desired nitrosamines in short reaction times (2 min) with excellent radiochemical conversion (>45%). Final radiotracers were obtained after purification in good radiochemical yields (>30%, decay corrected). Radiochemical purity was above 99% in all cases.

Efficient preparation of high-quality 64Cu for routine use

INTRODUCTION Copper-64 is an attractive radionuclide for positron emission tomography and is emerging as a radiotherapeutic agent. The demand of 64Cu with low metallic impurities has increased because of its wide applications when incorporated with antibodies, peptides, and proteins. In this study, we propose a new separation method to produce high-quality 64Cu using a cation exchange column, as well as an automated separation system suitable for large-scale production. METHODS 64Cu was produced from an electrodeposited 64Ni target via the 64Ni(p,n)-reaction with a 24MeV HH+ beam at 10eμA (electrical microampere) conducted for 1-3h. The irradiated target was transported to a hot cell and disassembled remotely. 64Cu was separated by a solvent mixture of HCl and acetone on a cation-exchange resin, AG50W-X8. The chemical purity of 64Cu final product was evaluated using ion-chromatography coupled with a UV detector and inductively coupled plasma mass spectroscopy for quality as well as metallic impurities. RESULTS We obtained 64Cu in dried form at a yield of 5.2-13GBq at the end of separation, or 521±12MBq/eμAh as the final product within 2.5h of processing time. The metallic impurities were a satisfactory low level in the order of ppb. Major contaminants of Co and Ni were lower than those samples obtained by a widely accepted separation using an anion-exchange resin. CONCLUSION Using a cation-exchange resin and a systematic operation, we successfully reduced the contamination level of the 64Cu product. As a straightforward separation method, which shortened the entire processing time, we obtained a satisfactory amount of high-quality 64Cu available for routine use.

Production of 211At by a vertical beam irradiation method

We produced (211)At by irradiating the semi-sealed encapsulated Bi target with an external vertical beam. At 28.5MeV, the yield of (211)At was 22MBq/μAh (600μCi/μAh). (211)At was recovered by dry distillation, and 80% of the produced (211)At was successfully obtained in dry Na(211)At form within 2h from the end of bombardment (EOB). The radionuclidic purity of (211)At was >99% at 5h from EOB.

An alumina ceramic target vessel for the remote production of metallic radionuclides by in situ target dissolution

INTRODUCTION As the use of metallic radionuclides increases, so does the demand for a simple production method. In this study, we demonstrated an in situ target processing concept for automated metallic radionuclide production without the use of any robotic device. METHODS An alumina ceramic vessel for a vertical irradiation system was designed and developed. The ceramic vessel was evaluated by the production of Zr-89 using an yttrium powder target. The irradiated Y was dissolved remotely in HCl in the ceramic vessel and transferred as a solution to a hotcell through a Teflon tube. The crude Zr-89 was then purified by an automated apparatus. The Zr-89 was eluted with 100 μL of oxalic acid (solution) as the final product. RESULTS The ceramic vessel gave a sufficient yield of Zr-89 (57±11MBq/μAh), showed good operability, and could be reused up to 10 times. With nominal irradiation (10μA×2h) in ~90 μL, the product (~940MBq) was obtained with >99.9% radionuclidic purity. CONCLUSION The combination of the ceramic vessel and vertical irradiation has great potential for the remote production of various metallic radionuclides.

11CH4 molecule production using a NaBH4 target for 11C ion accelerationa)

Solid-state materials suitable for use as proton irradiation targets were investigated for producing high-purity (11)CH4 molecules for heavy-ion cancer therapy. The radioactivity of gas produced by proton irradiation was measured for several target materials. Also, the radioactive molecular species of the produced gas were analyzed by radio gas chromatography. We found that 5 × 10(12) (11)C molecules could be collected by proton irradiation on a NaBH4 target. We also found that the (11)CH4 molecules were produced and collected directly from the irradiated target, owing to the hydrogen atoms bound in the solid-state NaBH4.

The use of tetrabutylammonium fluoride to promote N‐ and O‐11C‐methylation reactions with iodo[11C]methane in dimethyl sulfoxide

The N- or O-methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[(11) C]methane (1) with the aid of a base are frequently applied to the preparation of (11) C-labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated (11) C-methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for (11) C-methylation reactions using 1, studies concerning the use of TBAF to promote (11) C-methylation reactions are scarce. Herein, we have evaluated the efficiency of the (11) C-methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N-(11) C-methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O-(11) C-methylations required heating in some cases. Comparison studies revealed that the efficiencies of the (11) C-methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for (11) C-methylation reactions using 1.

Synthesis of 11C-labeled 2-aminoethanol via a nitroaldol reaction using nitro[11C]methane

The nitroaldol reaction of nitro[(11)C]methane and formaldehyde using EtOH and EtONa efficiently provided 2-nitro[(11)C]ethanol in 3min. The nitro group reduction in the presence of NiCl(2) and NaBH(4) in MeOH followed by purification using semi-preparative HPLC using 10% EtOH aqueous solution as an eluent proved to be a practical and accessible method for the synthesis of 2-amino[2-(11)C]ethanol.

Small-scale production of 67Cu for a preclinical study via the 64Ni(α, p)67Cu channel

INTRODUCTION Copper-67 is an attractive beta emitter for targeted radionuclide therapy. However, the availability of 67Cu limits its potential use in a wide range of applications. In this study, we propose an easy small-scale production of 67Cu using 64Ni target for a preclinical study. METHODS 67Cu was produced from an electrodeposited 64Ni target via the 64Ni(α, p)67Cu-reaction with a 36 MeV alpha beam at 15 eμA (electrical microampere) conducted for 7 h. The chemical separation process of 67Cu from the 64Ni target was performed following by our routine procedure of 64Cu production using cation exchange resin, AG50W-X8, with minor modification. The target and its holder were redesigned in the preparation. RESULTS The 67Cu product was obtained with a yield of 55 ± 10 MBq at the end of bombardment (EOB), and the yield was 527 ± 96 kBq/μAh at the EOB. The copper impurity in the product was low (0.71 ± 0.21 μg) and the product was suitable for a preclinical study. CONCLUSIONS We produced 67Cu with sufficient activity and quality for a preclinical study using a 64Ni-target. This production method also showed advantages as a routine method, i.e., shorten the processing time, reducing the radiation exposure and ready target recycling, when compared with that of a conventional Zn-target used for 67Cu production.

α-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10

Synovial sarcoma (SS) is a rare yet refractory soft‐tissue sarcoma that predominantly affects young adults. We show in a mouse model that radioimmunotherapy (RIT) with an α‐particle emitting anti‐Frizzled homolog 10 (FZD10) antibody, synthesized using the α‐emitter radionuclide astatine‐211 (211At‐OTSA101), suppresses the growth of SS xenografts more efficiently than the corresponding β‐particle emitting anti‐FZD10 antibody conjugated with the β‐emitter yettrium‐90 (90Y‐OTSA101). In biodistribution analysis, 211At was increased in the SS xenografts but decreased in other tissues up to 1 day after injection as time proceeded, albeit with a relatively higher uptake in the stomach. Single 211At‐OTSA101 doses of 25 and 50 μCi significantly suppressed SS tumor growth in vivo, whereas a 50‐μCi dose of 90Y‐OTSA101 was needed to achieve this. Importantly, 50 μCi of 211At‐OTSA101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of 90Y‐OTSA101. Both radiolabeled antibodies at the 50‐μCi dosage level significantly prolonged survival. Histopathologically, severe cellular damage accompanied by massive cell death was evident in the SS xenografts at even 1 day after the 211At‐OTSA101 injection, but these effects were relatively milder with 90Y‐OTSA101 at the same timepoint, even though the absorbed doses were comparable (3.3 and 3.0 Gy, respectively). We conclude that α‐particle RIT with 211At‐OTSA101 is a potential new therapeutic option for SS.