Facile One‐Pot Synthesis of Intrinsically Radiolabeled ⁶⁴Cu‐Human Serum Albumin Nanocomposite for Cancer Targeting

Abstract

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 64Cu metal nanoparticles capped within human serum albumin (HSA) scaffold (64Cu‐HSA nanocomposite). Detailed characterization of the as‐synthesized nanoparticles was carried out by various analytical techniques to establish the colloidal and radiochemical stability, biocompatibility and suitability for clinical administration. The biological efficacy of 64Cu‐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 nanoparticles for PET imaging.

Current outlook on radionuclide delivery systems: from design consideration to translation into clinics

“…The radiolabeling HSA-based NPs were also prepared using 99m Tc(CO) 3 + precursor, possessing the high affinity binding to the histidine residues on the protein surface [132]. The more recent method for obtaining radiolabeled HSA NPs was reported by Charkavarty et al [133]. Authors developed one-pot synthesis protocol fabrication of small sized (4–5 nm diameter), water-soluble, intrinsically radiolabeled 64 Cu metal NPs capped within HSA.…”

Facile One-Pot Synthesis of Intrinsically Radiolabeled and Cyclic RGD Conjugated 199Au Nanoparticles for Potential Use in Nanoscale Brachytherapy

“…The integral component of nanoscale brachytherapy involves design of functionalized nanoplatforms and development of suitable methodologies for radiolabeling of the same. In this regard, synthesis of intrinsically radiolabeled inorganic nanoparticles is an emerging concept that has shown attractive potential to offer facile, rapid, and more specific radiolabeling possibilities for the development of new generation radionanomedicine agents. − This novel approach overcomes inherent limitations of the classical radiolabeling strategy involving use of exogenous chelators that could coordinate with specific radioisotopes to form complexes. − In addition to providing enhanced in vitro and in vivo stabilities, intrinsically radiolabeled nanoparticles would potentially retain the native biodistribution and pharmacokinetics of the nanomaterial, thereby accurately reflecting its real in vivo behavior in living subjects . Moreover, this approach is easily executable in a hot cell facility under current good manufacturing practices (cGMP) compliant conditions, thus exhibiting tremendous prospective for future clinical translation.…”