Intrinsically Radioactive [⁶⁴Cu]CuInS/ZnS Quantum Dots for PET and Optical Imaging: Improved Radiochemical Stability and Controllable Cerenkov Luminescence

Abstract

Functionalized quantum dots (QDs) have been widely explored for multimodality bioimaging and proven to be versatile agents. Attaching positron-emitting radioisotopes onto QDs not only endows their positron emission tomography (PET) functionality, but also results in self-illuminating QDs, with no need for an external light source, by Cerenkov resonance energy transfer (CRET). Traditional chelation methods have been used to incorporate the radionuclide, but these methods are compromised by the potential for loss of radionuclide due to cleavage of the linker between particle and chelator, decomplexation of the metal, and possible altered pharmacokinetics of nanomaterials. Herein, we described a straightforward synthesis of intrinsically radioactive [64Cu]CuInS/ZnS QDs by directly incorporating 64Cu into CuInS/ZnS nanostructure with 64CuCl2 as synthesis precursor. The [64Cu]CuInS/ZnS QDs demonstrated excellent radiochemical stability with less than 3% free 64Cu detected even after exposure to serum containing EDTA (5 mM) for 24 h. PEGylation can be achieved in situ during synthesis, and the PEGylated radioactive QDs showed high tumor uptake (10.8% ID/g) in a U87MG mouse xenograft model. CRET efficiency was studied as a function of concentration and 64Cu radioactivity concentration. These [64Cu]CuInS/ZnS QDs were successfully applied as an efficient PET/self-illuminating luminescence in vivo imaging agents.

Photoluminescent nanoplatforms in biomedical applications

“…Combining PET with photoluminescent nanoparticles provides an opportunity to obtain more anatomical and physiological details by improving the spatial resolution. [138]. The QDs exhibited self-illuminating behavior without external source of excitation by effect of Cerenkov resonance energy transfer.…”

Multiplexed imaging for diagnosis and therapy

“…This strategy is embodied in both sequential and simultaneous multiplexed single-modality probes, for example by imaging the DNA repair system and its inhibition by targeting the enzyme poly ADP ribose polymerase (PARP) 68,69 ( Fig. 2a), as well as in multimodal nuclear OI probes, including small-molecule targeting of PARP1 in glioblastoma 70 , 111 In-DTPA-HQ4 71,72 in SPECT-OI of therapy-induced tumour necrosis, and numerous dual-labelled peptide 73,74 , antibody 75 , and nanoparticle probes 64,76,77 .…”

Review of biomedical Čerenkov luminescence imaging applications

“…This field is at an embryonic stage, and while the actual uses are likely to be in niche areas, the amount of physical chemistry research appears to be growing. Enhancement of the Čerenkov signal is possible via interaction with radiation absorbing media, such as gold or copper based nanoparticles [70][71][72]. Several innovative designs in nanoparticle material science have shown that a carefully designed particle can enhance the signal, or this effect could be used for microenvironment sensing [73].…”