Positron emission tomography (PET) is a quickly expanding, non-invasive molecular imaging technology, and there is high demand for new specific imaging probes. Herein, we present a generic protocol for direct radiolabeling of heat-sensitive biomolecules with the positron-emitting radioisotope fluorine-18 (¹⁸F) using the aluminum fluoride restrained complexing agent (Al¹⁸F-RESCA) method. The Al¹⁸F-RESCA method combines the chemical advantages of a chelator-based radiolabeling method with the unique physical properties of the radionuclide of choice, fluorine-18. Proteins of interest can be conjugated to RESCA via amine coupling using (±)-H₃RESCA-TFP, followed by purification using size-exclusion chromatography (SEC). Next, RESCA-derivatized biomolecules can be labeled in one step, at room temperature (~20 °C) in an aqueous medium with aluminum fluoride (Al¹⁸F). Al¹⁸F-labeled proteins can be obtained with moderate (12-17 GBq/µmol) to good (80-85 GBq/µmol) apparent molar activity, depending on the starting activity of ¹⁸F^-. In addition, satisfactory radiochemical yields (35-55%, non-decay corrected) and high radiochemical purity (>98%, using gel filtration or solid-phase purification) are obtained. The mild radiolabeling procedure takes 0.5 h to complete and can be used for direct labeling of vector molecules such as peptides, protein scaffolds, and engineered antibody fragments.

中文翻译：

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使用Al18F-RESCA方法对正电子发射断层显像成像的热敏生物分子进行直接氟18标记。

正电子发射断层扫描（PET）是一种快速扩展的非侵入性分子成像技术，并且对新的特定成像探头有很高的需求。在这里，我们提出了使用氟化铝约束的络合剂（Al ¹⁸ F-RESCA）方法用发射正电子的放射性同位素氟18（¹⁸ F）直接对热敏生物分子进行放射性标记的通用协议。Al ¹⁸ F-RESCA方法将基于螯合剂的放射性标记方法的化学优势与所选的放射性核素氟18的独特物理性质相结合。可以使用（±）-H ₃通过胺偶联将感兴趣的蛋白质与RESCA偶联RESCA-TFP，然后使用尺寸排阻色谱法（SEC）进行纯化。接下来，可在室温（〜20°C）下于氟化铝（Al ¹⁸ F）的水性介质中一步标记RESCA衍生的生物分子。根据¹⁸ F-的起始活性，可以获得中等（12-17 GBqq / µmol）至良好（80-85 GBq / µmol）表观摩尔活性的Al ¹⁸ F标记蛋白^。。此外，获得了令人满意的放射化学收率（35-55％，未进行衰变校正）和高放射化学纯度（> 98％，使用凝胶过滤或固相纯化）。温和的放射性标记过程需要0.5小时才能完成，可用于直接标记载体分子，例如肽，蛋白质支架和工程抗体片段。