Highly toxic alpha emitting radionuclide, astatine-211 (At) labelled compounds have great potential as therapeutic radiopharmaceuticals in the targeted alpha therapy (TAT). Previously we have reported the usefulness of copper (Cu)-mediated radiobromination and radioiodination via boronic acid precursors for the synthesis of Br/I-labelled prostate-specific membrane antigen (PSMA) inhibitors which are applicable as imaging probes. This background led us to investigate the Cu-mediated astatination of PSMA inhibitors as a therapeutic agent for TAT. At-labelled PSMA inhibitors [At]AtB-PS were synthesised from a boronic acid precursor with -butoxycarbonyl groups by Cu-mediated astatination in the presence or absence of NaOH and KCO in order to stabilize the chemical form of At followed by deprotection of the -butoxycarbonyl group under acidic condition. We confirmed that [At]AtB-PS was synthesised in 64.4–87.3% of overall radiochemical yields (RCYs). These yields are considered acceptable regardless of basic salts existed. However, RCYs of the astatination step differed depending on the base (NaOH: 22.0–31.9%; KCO; 69.0–82.3%; without base: 60.1%). We speculated that astatination also occurred during the deprotection of -butoxycarbonyl groups. This could be attributed to an electrophilic deboronation reaction involving electrophilic astatine species, resulting in compensation for the overall RCYs. Cu-mediated astatination via boronic precursors was found to be very effective for the synthesis of At-labelled PSMA inhibitors for the targeted alpha therapy.

中文翻译：

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碱式盐存在下铜介导的 211At 标记前列腺特异性膜抗原探针的砹化

高毒性α发射放射性核素、砹211 (At)标记的化合物作为靶向α疗法(TAT)中的治疗性放射性药物具有巨大潜力。此前，我们报道了通过硼酸前体铜（Cu）介导的放射性溴化和放射性碘化用于合成 Br/I 标记的前列腺特异性膜抗原（PSMA）抑制剂的有用性，该抑制剂可用作成像探针。这一背景促使我们研究铜介导的 PSMA 抑制剂作为 TAT 治疗剂的抑制作用。 At 标记的 PSMA 抑制剂 [At]AtB-PS 是通过在存在或不存在 NaOH 和 KCO 的情况下通过 Cu 介导的砹化作用从具有丁氧羰基的硼酸前体合成的，以稳定 At 的化学形式，然后脱保护酸性条件下的-丁氧基羰基。我们证实 [At]AtB-PS 的合成占总放射化学产率 (RCY) 的 64.4–87.3%。无论是否存在碱式盐，这些产率都被认为是可接受的。然而，砹化步骤的 RCY 根据碱的不同而不同（NaOH：22.0–31.9%；KCO；69.0–82.3%；无碱：60.1%）。我们推测在-丁氧羰基的脱保护过程中也发生了砹化。这可能归因于涉及亲电砹物质的亲电脱硼反应，从而补偿了总体 RCY。发现通过硼前体进行铜介导的砹化对于合成用于靶向α疗法的At标记的PSMA抑制剂非常有效。