Allott Louis, Dubash Suraiya, Aboagye Eric O
Comprehensive Cancer Imaging Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Cancers (Basel). 2020 Apr 2;12(4):865. doi: 10.3390/cancers12040865.
The success of Lutathera™ ([Lu]Lu-DOTA-TATE) in the NETTER-1 clinical trial as a peptide receptor radionuclide therapy (PRRT) for somatostatin receptor expressing (SSTR) neuroendocrine tumours (NET) is likely to increase the demand for patient stratification by positron emission tomography (PET). The current gold standard of gallium-68 radiolabelled somatostatin analogues (e.g., [Ga]Ga-DOTA-TATE) works effectively, but access is constrained by the limited availability and scalability of gallium-68 radiopharmaceutical production. The aim of this review is three-fold: firstly, we discuss the peptide library design, biological evaluation and clinical translation of [F]fluoroethyltriazole-βAG-TOCA ([F]FET-βAG-TOCA), our fluorine-18 radiolabelled octreotide; secondly, to exemplify the potential of the 2-[F]fluoroethylazide prosthetic group and copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry in accessing good manufacturing practice (GMP) compatible radiopharmaceuticals; thirdly, we aim to illustrate a framework for the translation of similarly radiolabelled peptides, in which in vivo pharmacokinetics drives candidate selection, supported by robust radiochemistry methodology and a route to GMP production. It is hoped that this review will continue to inspire the development and translation of fluorine-18 radiolabelled peptides into clinical studies for the benefit of patients.
Lutathera™（[Lu]Lu - DOTA - TATE）在NETTER - 1临床试验中作为一种用于表达生长抑素受体（SSTR）的神经内分泌肿瘤（NET）的肽受体放射性核素疗法（PRRT）取得成功，这可能会增加通过正电子发射断层扫描（PET）进行患者分层的需求。目前，镓 - 68放射性标记的生长抑素类似物（如[Ga]Ga - DOTA - TATE）这一金标准方法效果良好，但由于镓 - 68放射性药物生产的可用性和可扩展性有限，其应用受到限制。本综述的目的有三个方面：首先，我们讨论[F]氟乙基三唑 - βAG - TOCA（[F]FET - βAG - TOCA），即我们的氟 - 18放射性标记的奥曲肽的肽库设计、生物学评估和临床转化；其次，举例说明2 - [F]氟乙基叠氮化物基团和铜催化的叠氮化物 - 炔烃环加成（CuAAC）化学在获得符合药品生产质量管理规范（GMP）的放射性药物方面的潜力；第三，我们旨在阐述一个类似放射性标记肽的转化框架，其中体内药代动力学驱动候选物选择，并辅以稳健的放射化学方法和GMP生产途径。希望本综述能继续激发氟 - 18放射性标记肽的开发和转化，使其进入临床研究，造福患者。
