Поверхностное, с одним горшком синтез N-сукцинимидил-4-[<sup> 18</sup> F] fluorobenzoate ([<sup> 18</sup> F] SFB) был разработан на основе неводных, трехступенчатый радиохимического процесса. Использование микроволнового нагрева, вся процедура может быть завершена менее чем за 30 мин, или 60 мин с последующей очистки с помощью препаративной ВЭЖХ. Распад коррекцией радиохимического дает (RCYs) были 35-5% (п> 30).
Biomolecules, including peptides,1-9 proteins,10,11 and antibodies and their engineered fragments,12-14 are gaining importance as both potential therapeutics and molecular imaging agents. Notably, when labeled with positron-emitting radioisotopes (e.g., Cu-64, Ga-68, or F-18), they can be used as probes for targeted imaging of many physiological and pathological processes.15-18 Therefore, significant effort has devoted to the synthesis and exploration of 18F-labeled biomolecules. Although there are elegant examples of the direct 18F-labeling of peptides,19-22 the harsh reaction conditions (i.e., organic solvent, extreme pH, high temperature) associated with direct radiofluorination are usually incompatible with fragile protein samples. To date, therefore, the incorporation of radiolabeled prosthetic groups into biomolecules remains the method of choice.23,24
N-Succinimidyl-4-[18F]fluorobenzoate ([18F]SFB),25-37 a Bolton-Hunter type reagent that reacts with the primary amino groups of biomolecules, is a very versatile prosthetic group for the 18F-labeling of a wide spectrum of biological entities, in terms of its evident in vivo stability and high radiolabeling yield. After labeling with [18F]SFB, the resulting [18F]fluorobenzoylated biomolecules could be explored as potential PET tracers for in vivo imaging studies.1 Most [18F]SFB radiosyntheses described in the current literatures require two or even three reactors and multiple purifications by using either solid phase extraction (SPE) or high-performance liquid chromatography (HPLC). Such lengthy processes hamper its routine production and widespread applications in the radiolabeling of biomolecules. Although several module-assisted [18F]SFB syntheses have been reported,29-32, 41-42 they are mainly based on complicated and lengthy procedures using costly commercially-available radiochemistry boxes (Table 1). Therefore, further simplification of the radiosynthesis of [18F]SFB using a low-cost setup would be very beneficial for its adaption to an automated process.
Herein, we report a concise preparation of [18F]SFB, based on a simplified one-pot microwave-assisted synthesis (Figure 1). Our approach does not require purification between steps or any aqueous reagents. In addition, microwave irradiation, which has been used in the syntheses of several PET tracers,38-41 can gives higher RCYs and better selectivity than the corresponding thermal reactions or they provide similar yields in shorter reaction times.38 Most importantly, when labeling biomolecules, the time saved could be diverted to subsequent bioconjugation or PET imaging step.28,43 The novelty of our improved [18F]SFB synthesis is two-fold: (1) the anhydrous deprotection strategy requires no purification of intermediate(s) between each step and (2) the microwave-assisted radiochemical transformations enable the rapid, reliable production of [18F]SFB.
Эта упрощенная три шага, с одним горшком radiosynthesis из 18 F-ацилирования реагента [18 F] SFB разработан на основе неводных химии. Этот процесс имеет превосходную воспроизводимость и могут быть использованы для надежного производства [18 F] SFB в автоматизированных модулей радиох…
The authors have nothing to disclose.
Это исследование было поддержано Министерством энергетики США (DE-FG02-09ER09-08 и DE-PS02-09ER09-18), рака Йонссон всеобъемлющем центр в Лос-Анджелесе, и в отрасли университета Совместная исследовательская программа (UC Discovery Грант, bio07 -10 665). Мы благодарим доктора Nagichettiar Satyamurthy и штабов на установке UCLA биомедицинских Циклотрон для обеспечения F-18 радиоизотопных и много дискуссий проницательными. Мы благодарим доктора. Майкл Коллинз, Грег Леблан, Джозеф Ламберт, и Келлер Барнхардт от CEM за технические консультации и поддержку. Мы благодарим Дирк Уильямс, Уильямс Дарин, д-ра. Иосиф Hong Дун Лин, и Майкл Ван Дам для проектирования и обработки деталей для изменения реактора CEM микроволновой печью и для SPE модули очистки.
Name of the reagent | Company | Catalogue number | Comments (optional) |
acetic acid in aqueous solution (5%, v/v) | Fisher | A38-500 | Prepared in our lab |
Acetonitrile | Sigma-Aldrich | 75-05-8 | |
Diethyl ether | Sigma-Aldrich | 14775 | |
Dimethyl Sulfoxide (DMSO) | Sigma-Aldrich | 472301 | |
Ethyl 4-(N,N,N-trimethylammonium)benzoate triflate | Prepared in lab | ||
4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (K222) | Sigma-Aldrich | 29,111-0 | |
O-(N-succinimidyl)-N,N,N‘,N‘-tetramethyluronium tetrafluoroborate (TSTU) | Sigma-Aldrich | 105832-38-0 | |
Potassium carbonate in aqueous solution (1M) | Sigma-Aldrich | 209619 | Prepared in our lab |
Potassium tert-butoxide | Sigma-Aldrich | 156671 |