Review Article Radionanomedicine: Widened perspectives of molecular theragnosis Dong Soo Lee, M.D., Ph.D. a,b, ⁎ , Hyung-Jun Im, M.D. b , Yun-Sang Lee, Ph.D. a,b a Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea b Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea Received 21 August 2014; accepted 18 December 2014 Abstract Despite of promising preclinical results in the fields of in vivo theragnostics of nanomedicine, a majority of attempt for clinical translation has been blocked by unsolved concerns about possible hazards to human body. Theragnosis of nanomedicine relies on the property of huge surface area to volume ratio of nanomaterials, which can offer potential for multi-functionality. Radionanomedicine has a hybrid characteristic of tracer technology and multi-functionality. Thus, key advantage of radionanomedicine is a possibility of using low amount of nanomaterials for theragnosis. This review article focuses on the concept and advantages of radionanomedicine in theragnosis, formulation of radionanomaterials (particularly encapsulation method), in vivo biodistribution and excretion of radionanomaterials, and immune responses to radionanomaterials. From the Clinical Editor: The expansion of nanomedicine has recently seen the development of a new branch - radionanomedicine. The core concept of radionanomedicine relies on the labeling of radionuclides onto nanomaterials for use both in diagnosis and therapy. In this article, the authors gave a comprehensive review on the current status of radionanomedicine. This should provide interesting reading for practicing clinicians. © 2015 Elsevier Inc. All rights reserved. Key words: Nanomedicine; Radiolabeling; Theragnosis; Encapsulation; Biodistribution Nanomedicine consists of the following four disciplines: in vitro nanosensing and diagnostics, nanomolecular imaging, nano-targeted delivery, and tissue nano-engineering. Among them, in vivo theragnostics with or without imaging are related to nanomolecular imaging and nano-targeted delivery. It is predicted that in vitro diagnostics using nanotechnology will be used in clinical applications in the near future. Incremental values or comparative effectiveness of the new in vitro nanodiagnostic tools will determine their use. In contrast, in vivo theragnostics using nanotechnology meets objections or concerns about the possible hazards to humans and the environment. 1-4 There is a need to develop methods and ways to overcome the concerns about the toxic effects of the in vivo use of nanomaterials. The concept of radionanomedicine was recently presented as an extension of “targeted radionuclide therapy” in international symposia of the ICRT2012 (International Conference for Radiopharmaceutical Therapy), ISRS2013 (International Sym- posium of Radiopharmaceutical Sciences), 2014 international symposium of the NCC (National Cancer Center), and WCNMB2014 (World Congress of Nuclear Medicine and Biology). The core concept of radionanomedicine relies on both the labeling of radionuclides onto the nanomaterials and the use of trace amounts of radiolabeled nanomaterials for in vivo theragnostics. First, the labeling of nanomaterials with radionu- clides can be achieved in two ways: extrinsically, using chelators bound to the surface of nanomaterials, 5 and intrinsically, inside the nanoparticle 6,7 (Figure 1). Representative examples of intrinsically and extrinsically labeled nanoparticles are summa- rized in Table 1. Studies regarding intrinsically radiolabeled nanoparticles are well summarized in a recent review article by Goel et al. 52 In 2010, Zhou et al developed intrinsically 64 Cu-labeled copper sulfide (CuS) and the nanoparticle showed passive targeting in mouse tumor model. 8 In 2011, intrinsically radioactive upconverting nanoparticle, [ 18 F]-NaYF 4 :Gd,Yb,Er, was developed. 22 In 2014, Zhao et al developed a gold nanoparticle intrinsically labeled with 64 Cu and showed passive targeting of the nanoparticle to breast cancer mouse model. 10 Extrinsically labeled nanoparticles using chelators according to labeling methods and materials are well summarized in recent review articles by Xing et al 53 and Enrique et al 54 Chelators used Nanomedicine: Nanotechnology, Biology, and Medicine 11 (2015) 795 – 810 nanomedjournal.com Conflict of interest: The authors declare that they have no conflict of interest. ⁎ Corresponding author at: Department of Nuclear Medicine, Seoul National University Hospital 101 Daehangno Jongnogu, Seoul 110-744, Korea. E-mail address: dsl@plaza.snu.ac.kr (D.S. Lee). http://dx.doi.org/10.1016/j.nano.2014.12.010 1549-9634/© 2015 Elsevier Inc. All rights reserved. Please cite this article as: Lee DS, et al, Radionanomedicine: Widened perspectives of molecular theragnosis. Nanomedicine: NBM 2015;11:795-810, http://dx.doi.org/10.1016/j.nano.2014.12.010