Open camera or QR reader and scan code to access this article and other resources online. Potential Theranostic Boron Neutron Capture Therapy Agents as Multimodal Radiopharmaceuticals Amir R. Jalilian, 1 Arman Shahi, 2 Ian P. Swainson, 1 Hiroyuki Nakamura, 3 Meera Venkatesh, 1 and Joao A. Osso, Jr 1 Abstract Boron neutron capture therapy (BNCT) has been extant for decades and continues to be practiced in many centers around the globe. Most of the active clinical trials utilize boronophenylalanine as the drug containing boron atoms. The important aspect that has been added to the BNCT practice is the use of an F-18 radiolabeled analog for ascertaining targeting and monitoring follow-up studies. The recent widespread application of therapeutic radiopharmaceuticals, especially peptides (somatostatin analogs), prostate-specific antigen-binding ligands, or immunomolecules, offers the ambit for invention of new tumor-specific BNCT agents, especially for BNCT-susceptible tumors, that is, locoregional cancers such as head and neck cancer. Such BNCT agents, when radiolabeled, can enable simultaneous imaging and/or therapeutic applications (depending on the radionuclide used) through multimodal approaches. Development of boron-rich moieties such as sodium borocaptate and neutral carboranes combined with tumor-targeting moieties can lead to a new horizon in BNCT. The review covers various aspects of drug design, tumor targeting, and possible future radiopharmaceutical development for multimodal theranostic application in humans. Keywords: BNCT, boron compounds, BPA, BSH, peptides, radioisotopes, theranostic Introduction T he burden of cancer is daunting for the whole world as it is the second leading cause of death worldwide. 1 The current primary intervention methods such as radiotherapy, chemotherapy, and surgery have limited capacity for remedy. All these approaches have their limitations such as damage to surrounding cells in case of radiotherapy, development of drug resistance in chemotherapy, and tumor size restriction and approachability in the case of surgery, leaving some tu- mor cells behind. 2 In case of some malignancies such as gliomas, total eradication of the tumor without harming normal tissues presents a substantial barrier. 3 Boron neutron capture therapy (BNCT) is a technique that allows the therapy of tumor cells with minimal consequence to normal cells if adequate boron accumulation takes place in the target cell. However, it should be noted that sur- rounding normal cells will be exposed to neutrons and ionizing radiation, including protons resulting from the capture reaction with normal tissue nitrogen and recoil protons resulting from the collision of fast neutrons with hydrogen. The therapeutic ratio depends on tumor-specific accumulation of boron at concentrations high enough to make these contributions minimal. Since its conception, BNCT has been used to treat ma- lignant melanomas, malignant brain tumors with or without 1 Nuclear Sciences and Applications Department, International Atomic Energy Agency, Vienna, Austria. 2 Faculty of Science, McMaster University, Hamilton, Canada. 3 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan. Address correspondence to: Amir R. Jalilian; Nuclear Sciences and Applications Department, International Atomic Energy Agency; Vienna 1220, Austria E-mail: a.jalilian@iaea.org CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Volume 37, Number 5, 2022 ª Mary Ann Liebert, Inc. DOI: 10.1089/cbr.2021.0276 342 Downloaded by 52.90.221.114 from www.liebertpub.com at 01/13/24. For personal use only.