The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. A BFC derived from the DATA ligand (2,2’-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2–4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = −3.2 ± 0.3, with a HPLC retention time (t R = 10.4 min) similar to 68Ga-DOTATOC (logP = −2.9 ± 0.4, t R = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards.

中文翻译：

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DATATOC：一种新型偶联物，用于在环境温度下对 TOC 进行试剂盒型 68Ga 标记。

68Ga-PET 的广泛接受和应用取决于我们开发能够以方便和合适的方式制备的放射性药物的能力。试剂盒类型的标记方案提供了这样的特性，并且需要可以在异常温和的条件下进行放射性标记的螯合剂。最近推出了满足这些要求的 DATA 螯合剂。在继续开发过程中，描述了第一个 DATA 双功能螯合剂 (BFC) 和肽缀合物的合成和放射性标记。衍生自 DATA 配体 (2,2'-(6-((羧甲基)氨基)-1,4-二氮杂-1,4-二基)二乙酸) 的 BFC 由简单的结构单元分五步合成，具有总产率为 8%。DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4] diazepan-6-yl]-pentanoic acid) 已与 [DPhe1][Tyr3]-octreotide (TOC) 偶联，得到的肽偶联物 (DATATOC) 用通过四种不同的 68Ge/68Ga 发生器后处理衍生的纯化 68Ga 进行放射性标记(PP) 方法。已经评估了放射性示踪剂的稳定性和亲脂性，并评估了用于放射性标记的试剂盒型制剂。68Ga-DATATOC 在 23 °C（pH 4.2–4.9, 13 nmol）下 1（分馏和丙酮-PP）和 10 分钟（乙醇和 NaCl-PP）内以 > 95% 的放射化学产率 (RCY) 制备。放射性标记的肽在人血清存在下是稳定的。68Ga-DATATOC 的亲脂性计算为 logP = -3.2 ± 0.3，HPLC 保留时间 (t R = 10.4 min) 与 68Ga-DOTATOC (logP = -2.9 ± 0.4, t R = 10.3 min) 相似。使用基于丙酮-PP 的标记对冻干固体进行试剂盒型标记，在 23 °C 下 10 分钟内可实现 > 95 % RCY。DATATOC 保留了 DATA 螯合剂的良好标记特性。在 23 °C 下，不到 1 分钟即可通过试剂盒配方实现高放射化学纯度。可以制备 68Ga-DATATOC 的速度、可靠性、易用性、灵活性和简单性使其成为当前标准的非常有吸引力的替代品。