Improved Stability and Practicality for Synthesis of 4-Borono-2-[18F]fluoro-l-phenylalanine by Combination of [18O]O2 Single-Use and [18F]CH3COOF Labeling Agents

Sadahiro Naka,Mitsuaki Tatsumi,Tadashi Watabe,Jun Hatazawa,Toshimitsu Watanabe,Yasukazu Kanai,Eku Shimosegawa,Hiroki Kato

doi:10.1007/s13139-021-00719-1

Abstract

Purpose4-Borono-2-[18F]fluoro-l-phenylalanine ([18F]FBPA) synthesized with [18F]F2, produced using the 18O(p, n)18F reaction, has been reported for increasing radioactivity. However, a dedicated system and complex procedure is required to reuse the costly [18O]O2 gas; also, the use of [18F]F2 as a labeling agent reduces the labeling rate and radiochemical purity. We developed a stable and practical method for [18F]FBPA synthesis by combining [18F]F2, produced using a [18O]O2 single-use system, and a [18F]CH3COOF labeling agent.MethodsThe produced [18F]F2 was optimized, and then [18F]FBPA was synthesized. For passivation of the target box, 0.5% F2 was pre-irradiated in argon. Gaseous products were discarded; the target box was filled with [18O]O2 gas, and then irradiated (first irradiation). Then, the [18O]O2 gas was discarded, 0.05–0.08% F2 in argon was fed into the target box, and it was again irradiated (second irradiation). The [18F]F2 obtained after this was passed through a CH3COONa column, converting it into the [18F]CH3COOF labeling agent, which was then used for [18F]FBPA synthesis.ResultsThe mean amount of as-obtained [18F]F2 was 55.0 ± 3.3 GBq and that of as-obtained [18F]CH3COOF was 21.6 ± 1.4 GBq after the bombardment. The radioactivity and the radiochemical yield based on [18F]F2 of [18F]FBPA were 4.72 ± 0.34 GBq and 12.2 ± 0.1%, respectively. The radiochemical purity and molar activity were 99.3 ± 0.1% and 231 ± 22 GBq/mmol, respectively.ConclusionWe developed a method for [18F]FBPA production, which is more stable and practical compared with the method using [18O]O2 gas-recycling and [18F]F2 labeling agent.

Highlights

Material and MethodsBoron neutron capture therapy (BNCT) is an anti-cancer treatment that is based on the 10B(n, α)7Li reaction in tumors, and the high linear energy transfer of the α and 7Li particles generated upon the irradiation of 10B [1,2,3,4].Recently, the BNCT system was approved as a medical device for neutron irradiation, and 10B-4-borono-L-phenylalanine (10BPA) was approved as a 10B-carrier-drug for cancer cells, by the Ministry of Health, Labour and Welfare in Japan
We developed a method for producing [18F]FBPA through the nuclear reaction of 18O(p, n)18F using the existing target, Fig. 4 Radioactivity of [18F]F2 at each fluorine concentration in the target (0–0.9%); radioactivity of [18F]F2 after second irradiation at 17 μA for 10 min which does not require the use of a [18O2]O2 gas-recycling system for [18F]F2 production, and employs [18F]CH3COOF as the labeling agent
We used 0.05–0.08% of the F2 carrier gas to obtain the maximum amount of [18F]F2 with a high molar activity. In this highvolume target box, the amount of [18F]F2 positively correlated with the intensity of the proton beam and irradiation time, which was in good agreement with the results reported by

Summary

Introduction

Boron neutron capture therapy (BNCT) is an anti-cancer treatment that is based on the 10B(n, α)7Li reaction in tumors, and the high linear energy transfer of the α and 7Li particles generated upon the irradiation of 10B [1,2,3,4]. The BNCT system was approved as a medical device for neutron irradiation, and 10B-4-borono-L-phenylalanine (10BPA) was approved as a 10B-carrier-drug for cancer cells, by the Ministry of Health, Labour and Welfare in Japan. The availability of [18F]FBPA is critical to the successful determination of the cellular 10B levels to ensure treatment efficacy, and several approaches have been reported to address its synthesis.

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