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

Abstract

Purpose 4-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. Methods The 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. Results The 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. Conclusion We 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.

Advantages of FBPA PET in evaluating early response of anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice: Comparison to FDG PET

“…[ 18 F]FBPA was synthesized according to previous report ( 9 ). In short, [ 18 F]FBPA was produced by reacting a precursor solution (30 mg of 4-borono-L-phenylalanine in 4 mL trifluoroacetic acid) with [ 18 F]acetylhypofluorite.…”

Evaluation of LAT1 Expression in Patients With Lung Cancer and Mediastinal Tumors

“…The 18 F-FBPA solution was synthesized using a CFN-MPS200 (Sumitomo Heavy Industries, Tokyo, Japan) based on a previous study. 14 In brief, 18 F-CH 3 COOF, obtained by passing 18 F-F 2 gas through a sodium acetate column, was reacted with 4-borono-L-phenylalanine dissolved in trifluoroacetic acid for the synthesis of 18 F-FBPA. After 18 F-FBPA was separated and purified by high-performance liquid chromatography and evaporation, it was dissolved in normal saline and then collected through a sterile 0.22 μm vented millex-GS filter into a sterile vial.…”

Clinical Use of Radiopharmaceuticals in Boron Neutron Capture Therapy

“…And we expect that PET/MR researches in Japan will be more popular and useful [1]. Recent research of Prof. Hatazawa's group on more practical and stable production method for [ 18 F]FBPA compared with the method using [ 18 O]O2 gas-recycling and [ 18 F]F2 labeling agent is published in the issue of NMMI [2]. We think that it is time to pay attention to BNCT.…”

“…Still we need more study about that. Fortunately, Prof. Hatazawa's group developed a practical method of producing [ 18 F]FBPA with better stability and usefulness than the methods of [ 18 O]O 2 gas-recycling and [ 18 F]F 2 labeling [2]. We know that [ 18 F]FBPA is a new radiopharmaceutical, which means that it takes a long time to obtain the approval of authorization body, Ministry of Food and Drug Safety and the cost of production depends on the efficiency of method.…”

“…Likewise, the use of [ 18 F]FBPA ratio will provide us with more information about the preparation of BNCT and the evaluation of a prognosis. In this issue, Prof. Hatazawa's group introduced the synthesis of [ 18 F]FBPA with improved stability and practicality [2]. It is expected to be used in clinical routine.…”