REVIEW article
Front. Oncol.
Sec. Radiation Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1572118
An overview of the role of radionuclides in targeted cancer treatment: application of biomarkers for patient selection and developments to improve treatment efficacy
Provisionally accepted
- 1The University of Manchester, Manchester, United Kingdom
- 2Bangor University, Bangor, Wales, United Kingdom
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Radiopharmaceuticals for targeted radionuclide therapy (TRT) of tumours consist of a radionuclide conjugated to a component that can target the cancer. Several TRT radiopharmaceuticals have been licensed for the treatment of lymphoma, neuroendocrine and prostate cancer. The outcomes from two TRT trials, NETTER for neuroendocrine and VISION for prostate cancer demonstrated beneficial outcomes. These findings have increased interest in the application of TRT in the treatment of prostate cancer and expansion to other cancer types. Patient selection for TRT is based on a measure of the overexpression of a target receptor on the cancer. To facilitate this, imaging is carried out using a similar targeting moiety to that used for treatment but labelled with an imaging radionuclide. Theragnostic pairs are selected to enable imaging and treatment with the same construct providing accurate predictions of the pharmacokinetics of the therapeutic in patients. This review covers the imaging biomarkers that act as companion diagnostics for TRT pharmaceuticals and the development of radiopharmaceuticals targeting other cancer types enabling expansion of TRT to these cancers. These include strategies to target cancer cells specifically and a pan-cancer approach by targeting fibroblast activated protein (FAP) upregulated on cancer associated fibroblasts (CAF). FAP-targeted radiopharmaceuticals are useful for diagnosis and staging but have drawbacks for TRT. Approaches to improve efficacy of TRT including the use of high linear energy transfer (LET) alpha-emitters, pre-targeting and combination treatments are also covered. As described in this review not all patients benefit from TRT making the case for predictive biomarkers. This is particularly important for the more damaging alpha emitters.
Keywords: targeted radionuclide therapy, radionuclide, antibody, Cancer, PSMA, biomarker, radiosensitiser
Received: 06 Feb 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tim Andrew Davies Smith, The University of Manchester, Manchester, United Kingdom
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