Combination Strategies to Improve Targeted Radionuclide Therapy

• Published in: Journal of Nuclear Medicine Vol. 61; no. 11; pp. 1544 - 1552
• Main Authors: Chan, Tiffany G, O'Neill, Edward, Habjan, Christine, Cornelissen, Bart
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.11.2020
• Subjects: Addition polymerization; Adenosine; Adenosine diphosphate; Cell Cycle - drug effects; Chemical compounds; Chemotherapy; Clinical trials; Combined Modality Therapy; DNA Damage; DNA Repair - drug effects; Dosage; Hedgehog Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - antagonists & inhibitors; Humans; Immune Checkpoint Inhibitors - therapeutic use; Ionizing radiation; Lymphoma; NAD - metabolism; Neoplasms - radiotherapy; Neuroblastoma; Neuroendocrine tumors; Non-Hodgkin's lymphoma; Octreotide - analogs & derivatives; Octreotide - therapeutic use; Organometallic Compounds - therapeutic use; Pharmacology; Public domain; Radiation therapy; Radiation-Sensitizing Agents - pharmacology; Radiation-Sensitizing Agents - therapeutic use; Radioisotopes; Radiosensitizers; Rapamycin; Ribose; The State of the Art; Topoisomerase Inhibitors - pharmacology; Topoisomerase Inhibitors - therapeutic use; TOR Serine-Threonine Kinases - antagonists & inhibitors; Toxicity; Tumors; radiotherapy; targeted radionuclide therapy; combination therapy
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.120.248062

In recent years, targeted radionuclide therapy (TRT) has emerged as a promising strategy for cancer treatment. In contrast to conventional radiotherapy, TRT delivers ionizing radiation to tumors in a targeted manner, reducing the dose that healthy tissues are exposed to. Existing TRT strategies include the use of Lu-DOTATATE, I-metaiodobenzylguanidine, Bexxar, and Zevalin, clinically approved agents for the treatment of neuroendocrine tumors, neuroblastoma, and non-Hodgkin lymphoma, respectively. Although promising results have been obtained with these agents, clinical evidence acquired to date suggests that only a small percentage of patients achieves complete response. Consequently, there have been attempts to improve TRT outcomes through combinations with other therapeutic agents; such strategies include administering concurrent TRT and chemotherapy, and the use of TRT with known or putative radiosensitizers such as poly(adenosine diphosphate ribose) polymerase and mammalian-target-of-rapamycin inhibitors. In addition to potentially achieving greater therapeutic effects than the respective monotherapies, these strategies may lead to lower dosages or numbers of cycles required and, in turn, reduce unwanted toxicities. 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. Although some clinical trials have yielded promising results, others have shown no clear survival benefit from 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.