Combination Strategies to Improve Targeted Radionuclide Therapy.

In recent years, targeted radionuclide therapy (TRT) has emerged as a promising strategy for cancer treatment. In contrast to conventional radiotherapy, TRT delivers ionising radiation to tumours in a targeted manner, reducing the dose that healthy tissues are exposed to. Existing TRT strategies include the use of 177Lu-DOTATATE and 131I-MIBG, FDA-approved agents for the treatment of neuroendocrine tumours, and 177Lu-PSMA, which is being investigated for the treatment of prostate cancer. Although promising results have been obtained with these agents, clinical evidence acquired to date suggests that only a small percentage of patients achieve complete response. Consequently, there have been attempts to improve the efficacy of TRT through combinations with other therapeutic agents; such strategies include administering concurrent TRT and chemotherapy, and the use of TRT with known or putative radiosensitisers such as PARP and mTOR inhibitors. In addition to potentially achieving greater therapeutic effects than the respective monotherapies, these strategies may lead to lower dosages or number of cycles required and, in turn, reduce unwanted toxicities and reduce costs for healthcare providers. As of now, several clinical trials have been conducted to assess the benefits of TRT-based combination therapies, sometimes despite limited preclinical evidence being available in the public domain to support their use. Whilst some clinical trials have yielded promising results, others have shown no clear survival benefit of particular combination treatments. Here, we present a comprehensive review of combination strategies with TRT reported in the literature to date and evaluate their therapeutic potential.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020 Oct 09 [Epub ahead of print]

Tiffany Chan, Edward O'Neill, Christine Habjan, Bart Cornelissen

MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, United Kingdom., MRC Institute for Radiation Oncology, Department of Oncology, University of Oxford, United Kingdom.

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