Oxalic Acid Supported Si鈥?sup>18F-Radiofluorination: One-Step Radiosynthesis of N-Succinimidyl 3-(Di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for Prote

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• 作者：Alexey P. Kostikov ; Joshua Chin ; Katy Orchowski ; Sabrina Niedermoser ; Miriam M. Kovacevic ; Antonio Aliaga ; Klaus Jurkschat ; Bjoern W盲ngler ; Carmen W盲ngler ; Hans-J眉rgen Wester ; Ralf Schirrmacher
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：January 18, 2012
• 年：2012
• 卷：23
• 期：1
• 页码：106-114
• 全文大小：391K
• 年卷期：v.23,no.1(January 18, 2012)
• ISSN：1520-4812

文摘

N-Succinimidyl 3-(di-tert-butyl[¹⁸F]fluorosilyl)benzoate ([¹⁸F]SiFB), a novel synthon for one-step labeling of proteins, was synthesized via a simple ¹⁸F鈥?sup>19F isotopic exchange. A new labeling technique that circumvents the cleavage of the highly reactive active ester moiety under regular basic ¹⁸F-labeling conditions was established. In order to synthesize high radioactivity amounts of [¹⁸F]SiFB, it was crucial to partially neutralize the potassium oxalate/hydroxide that was used to elute ¹⁸F^{鈥?/sup> from the QMA cartridge with oxalic acid to prevent decomposition of the active ester moiety. Purification of [18F]SiFB was performed by simple solid-phase extraction, which avoided time-consuming HPLC and yielded high specific activities of at least 525 Ci/mmol and radiochemical yields of 40鈥?6%. In addition to conventional azeotropic drying of 18F鈥?/sup> in the presence of [K+2.2.2.]C₂O₄, a strong anion-exchange (SAX) cartridge was used to prepare anhydrous 18F鈥?/sup> for nucleophilic radio-fluorination omitting the vacuum assisted drying of 18F鈥?/sup>. Using a lyophilized mixture of [K+2.2.2.]OH resolubilized in acetonitrile, the 18F鈥?/sup> was eluted from the SAX cartridge and used directly for the [18F]SiFB synthesis. [18F]SiFB was applied to the labeling of various proteins in likeness to the most commonly used labeling synthon in protein labeling, N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Rat serum albumin (RSA), apo-transferrin, a 尾-cell-specific single chain antibody, and erythropoietin were successfully labeled with [18F]SiFB in good radiochemical yields between 19% and 36%. [18F]SiFB- and [18F]SFB-derivatized RSA were directly compared as blood pool imaging agents in healthy rats using small animal positron emission tomography. Both compounds demonstrated identical biodistributions in healthy rats, accurately visualizing the blood pool with PET.}