1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Materials Science inc. Nanomaterials & Polymers Facile One-Pot Synthesis of Intrinsically Radiolabeled 64 Cu-Human Serum Albumin Nanocomposite for Cancer Targeting Rubel Chakravarty,* [a] Sudipta Chakraborty, [a] Apurav Guleria, [b] Amit Kunwar, [b] Haladhar Dev Sarma, [c] and Ashutosh Dash [a] Development of suitably radiolabeled nanoplatforms for cancer targeting is still at an early stage necessitating a simplified and reliable approach for incorporation of radioisotopes onto nanoparticles with minimal impact on their original biological behavior. In this study, we have developed an one-pot synthesis protocol for preparation of small sized (4-5 nm diameter), water soluble, intrinsically radiolabeled 64 Cu metal nanoparticles capped within human serum albumin (HSA) scaffold ( 64 Cu-HSA nanocomposite). Detailed characterization of the as-synthesized nanoparticles was carried out by various analytical techniques to establish the colloidal and radiochemical stability, biocom- patibility and suitability for clinical administration. The bio- logical efficacy of 64 Cu-HSA nanocomposite was demonstrated by biodistribution studies in melanoma tumor bearing C57BL/6 mice, that showed rapid diffusion and accumulation of the radiotracer into tumor and clearance from the biological system by both renal and hepatobiliary routes. The promising results obtained in this study suggest that this strategy could be employed to facilitate clinical translation of a new class of biocompatible radiotracers derived from metal-based nano- particles for PET imaging. Introduction Over the last decade, advances in nanomedicine have slowly been translated into significant clinical developments, espe- cially for cancer care. [1] The recent progress toward synthesis of functionalized nanoplatforms holds tremendous promise not only in early diagnosis of cancer but also in targeted delivery of therapeutic agents to cancerous lesions, such that the harmful side effects of conventional anti-cancer strategies could be significantly decreased. [1b,2] The overwhelming interest and considerable investment made in nanomedical applications worldwide is primarily attributed to the unique characteristics of the nanoplatforms which offer the ability to fulfil unmet medical needs and provide a cost-effective outlook in disease management. With the recent evolution of radiolabeled nanoparticles as a new frontier in cancer nanomedicine, several key challenges in early cancer detection and monitoring the efficacy of therapeu- tic protocols could be effectively addressed which ultimately might pave the way toward “personalized” cancer management in foreseeable future. [3] Despite availability of an extensive volume of literature, [3a,4] successful development of a radio- labeled nanoplatform is still a non-trivial issue and deserves careful thought, which involve, rational selection of the radio- isotope, suitability of the radiolabeling strategy and the choice of the nanoplatform. Matching the physical half-life of the radioisotope with the biological half-life of the radiolabeled agent is another important aspect in cancer theranostics, especially while using functionalized nanoplatforms with ex- tended circulation in vivo. Several strategies have been reported for radiolabeling of nanoparticles, each with its characteristic advantages and limitations. [4a] Among them, the concept of intrinsically radio- labeled nanoparticles is gaining prominence in the recent times, particularly because it results in nanoformulations with high in vitro and in vivo stability and excellent radiolabeling yields. [5] This approach is easily amenable for scale-up to achieve synthesis of clinically relevant doses of the radiolabeled nanoplatform. However, the entire synthesis process must be executed in a hot-cell equipped with remotely operable gadgets in order to minimize radiation exposure to the working personnel. This essentially mandates that the synthesis proce- dure should be facile in order to obtain the radiolabeled nanoparticles with desired characteristics in minimum number of steps. Copper-64 (t1 = 2 = 12.7 h., b + 17.9%, E.C. 45%, b À 37.1%), is a unique intermediate half-lived radioisotope which decays by three processes, namely, electron capture, b + and b À decays. [6] Owing to simultaneous emission of b + and b À particles, this [a] Dr. R. Chakravarty, Dr. S. Chakraborty, Dr. A. Dash Radiopharmaceuticals Division Bhabha Atomic Research Centre Trombay, Mumbai 400 085, India E-mail: rubelc@barc.gov.in [b] Dr. A. Guleria, Dr. A. Kunwar Radiation and Photochemistry Division Bhabha Atomic Research Centre Trombay, Mumbai 400 085, India [c] Dr. H. D. Sarma Radiation Biology and Health Sciences Division Bhabha Atomic Research Centre Trombay, Mumbai 400 085, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201701237 Full Papers DOI: 10.1002/slct.201701237 8043 ChemistrySelect 2017, 2, 8043 – 8051  2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim