Comparative Oncology Radiobiology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, USA.
Vet Comp Oncol. 2024 Jun;22(2):165-173. doi: 10.1111/vco.12969. Epub 2024 Mar 5.
Advancements in molecular imaging and drug targeting have created a renaissance in the development of radiopharmaceuticals for therapy and theranostics. While some radiopharmaceuticals, such as Na[I]I, have been used clinically for decades, new agents are being approved using small-molecules, peptides, and antibodies for targeting. As these agents are being developed, the need to understand dosimetry and biologic effects of the systemically delivered radiotherapy becomes more important, particularly as highly potent radiopharmaceuticals using targeted alpha therapy become clinically utilized. As the processes being targeted become more complex, and the radiobiology of different particulate radiation becomes more diverse, models that better recapitulate human cancer and geometry are necessary. Companion animals develop many of the same types of cancer, carrying many of the same genetic drivers as those seen in people, and the scale and geometry of tumours in dogs more closely mimics those in humans than murine tumour models. Key translational challenges in oncology, such as alterations in tumour microenvironment, hypoxia, heterogeneity, and geometry are addressed by companion animal models. This review paper will provide background on radiopharmaceutical targeting techniques, review the use of radiopharmaceuticals in companion animal oncology, and explore the translational value of treating these patients in terms of dosimetry, treatment outcomes, and normal tissue complication rates.
分子影像学和药物靶向技术的进步，为治疗和诊断放射性药物的发展带来了复兴。虽然一些放射性药物，如 Na[I]I，已经在临床上使用了几十年，但新的药物正在通过小分子、肽和抗体等靶向药物获得批准。随着这些药物的开发，了解全身放射性治疗的剂量学和生物学效应变得更加重要，特别是当使用靶向α治疗的高活性放射性药物在临床上得到应用时。随着靶向的过程变得更加复杂，以及不同的粒子辐射的放射生物学变得更加多样化，需要更好地模拟人类癌症和几何形状的模型。与啮齿动物肿瘤模型相比，患有许多相同类型癌症的伴侣动物携带与人类相同的遗传驱动因素，并且狗的肿瘤的规模和几何形状更接近人类。肿瘤微环境、缺氧、异质性和几何形状等肿瘤学中的关键转化挑战，都可以通过伴侣动物模型来解决。本文综述了放射性药物靶向技术，回顾了放射性药物在伴侣动物肿瘤学中的应用，并探讨了从剂量学、治疗结果和正常组织并发症率方面治疗这些患者的转化价值。
