Oncological pretargeting has been implemented and tested in several different ways in preclinical models and clinical trials over more than 30 years. Despite highly promising results, pretargeting has not achieved market approval even though it could be considered the ultimate theranostic, combining PET imaging with short-lived positron emitters and therapy with radionuclides emitting beta or alpha particles. We have reviewed the pretargeting approaches proposed over the years, discussing their suitability for imaging, particularly PET imaging, and therapy, as well as their limitations. The reviewed pretargeting modalities are the avidin-biotin system, bispecific anti-tumour x anti-hapten antibodies and bivalent haptens, antibody-oligonucleotide conjugates and radiolabelled complementary oligonucleotides, and approaches using click chemistry. Finally, we discuss recent developments, such as the use of small binding proteins for pretargeting that may offer new perspectives to cancer pretargeting. While pretargeting has shown promise and demonstrated preclinical and clinical proof of principle, full-scale clinical development programs are needed to translate pretargeting into a clinical reality that could ideally fit into current theranostic and precision medicine perspectives.

中文翻译：

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肿瘤核医学成像和治疗的预靶向。

30 多年来，肿瘤预靶向已在临床前模型和临床试验中以多种不同方式实施和测试。尽管取得了非常有希望的结果，但预靶向尚未获得市场认可，尽管它可以被认为是最终的治疗诊断，将 PET 成像与短寿命的正电子发射器结合起来，并用发射 β 或 α 粒子的放射性核素进行治疗。我们回顾了多年来提出的预靶向方法，讨论了它们对成像，特别是 PET 成像和治疗的适用性，以及它们的局限性。审查的预靶向模式是亲和素-生物素系统、双特异性抗肿瘤 x 抗半抗原抗体和二价半抗原、抗体-寡核苷酸偶联物和放射性标记的互补寡核苷酸，以及使用点击化学的方法。最后，我们讨论了最近的发展，例如使用小结合蛋白进行预靶向，这可能为癌症预靶向提供新的视角。虽然预靶向已显示出前景并证明了临床前和临床原理证明，但需要全面的临床开发计划将预靶向转化为临床现实，以理想地适应当前的治疗诊断和精准医学观点。