Efficient gallium‐68 radiolabeling reaction of DOTA derivatives using a resonant‐type microwave reactor

• Published in: Journal of labelled compounds & radiopharmaceuticals 2019-03, Vol.62 (3), p.132-138
• Main Authors: Yagi, Yusuke, Shimizu, Yoichi, Arimitsu, Kenji, Nakamoto, Yuji, Higuchi, Takahiro, Togashi, Kaori, Kimura, Hiroyuki
• Format: Article
• Language: English
• Subjects: 68Ga‐chelation; 68Ga‐DOTA–TOC; 68Ga‐p‐Bn–NCS–DOTA; Chelates; Chelating Agents - chemistry; Chelation; Chemistry Techniques, Synthetic - instrumentation; Chemistry Techniques, Synthetic - methods; Gallium; Gallium Radioisotopes - chemistry; Heating; Heterocyclic Compounds, 1-Ring - chemistry; High temperature; Microwaves; Positron emission; Positron emission tomography; positron emission tomography radiochemistry; Radiochemistry; Radiolabelling; Radiopharmaceuticals - chemical synthesis; Reaction time; resonant‐type microwave reactor; Temperature requirements; Tomography
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3704

Gallium‐68 (68Ga, t1/2 = 68 min) can be easily obtained from a 68Ge/68Ga generator, and several such systems are commercially available. The use of positron emission tomography (PET) imaging using 68Ga‐labeled radiopharmaceuticals is expected to increase in both preclinical and clinical settings. However, the chelation between a 68Ga cation and the bifunctional macrocyclic chelates that are used for labeling bioactive substances, such as 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA), requires a relatively long reaction time and high temperature to achieve a high radiochemical yield. Previously, we reported on a novel resonant‐type microwave reactor that can be used for radiosynthesis and the usefulness of this reactor in the PET radiosynthesis of 18F. In the present study, the usefulness of this resonant‐type microwave reactor was evaluated for the radiolabeling of model macrocyclic chelates with 68Ga. As a result, microwave heating of resonant‐type microwave reactor notably improved the rate of the 68Ga labeling chelate reaction in a short time period of 2 minutes, compared with the use of a conventional heating method. Additionally, it was found that the use of this reactor made it possible to decrease the amount of precursors required in the reaction and to improve the molar activity of the labeled compounds. In the synthetic study of [68Ga]p‐Bn–NCS–DOTA and [68Ga]DOTA–TOC, we found that microwave heating using the resonant‐type microwave reactor notably improved the rate of the 68Ga labeling chelate reaction for 2 minutes, compared with the use of a conventional heating method. Additionally, it was found that the use of this reactor made it possible to decrease the amount of precursors required in the reaction and to improve the specific activity of the labeled compounds.