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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 [(64)Cu]CuInS/ZnS QDs by directly incorporating (64)Cu into CuInS/ZnS nanostructure with (64)CuCl2 as synthesis precursor. The [(64)Cu]CuInS/ZnS QDs demonstrated excellent radiochemical stability with less than 3% free (64)Cu 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 (64)Cu radioactivity concentration. These [(64)Cu]CuInS/ZnS QDs were successfully applied as an efficient PET/self-illuminating luminescence in vivo imaging agents.

SUBMITTER: Guo W

PROVIDER: S-EPMC4310640 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Intrinsically radioactive [64Cu]CuInS/ZnS quantum dots for PET and optical imaging: improved radiochemical stability and controllable Cerenkov luminescence.

Guo Weisheng W Sun Xiaolian X Jacobson Orit O Yan Xuefeng X Min Kyunghyun K Srivatsan Avinash A Niu Gang G Kiesewetter Dale O DO Chang Jin J Chen Xiaoyuan X

ACS nano 20150102 1

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 po ...[more]

PMID: 25549258

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Project description:The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies.In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters (18)F, (64)Cu, (89)Zr, and (124)I; beta-emitter (131)I; and alpha-particle emitter (225)Ac for potential use in CLI. The novel radiolabeled monoclonal antibody (89)Zr-desferrioxamine B [DFO]-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies.Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-, beta-, and alpha-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of (89)Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities.These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear tomographic imaging and radiotherapy have the potential to be used in CLI. The value of CLI lies in its ability to image radionuclides that do not emit either positrons or gamma-rays and are, thus, unsuitable for use with current nuclear imaging modalities. Optical imaging of Cerenkov radiation emission shows excellent promise as a potential new imaging modality for the rapid, high-throughput screening of radiopharmaceuticals.

Dataset Information

Intrinsically radioactive [64Cu]CuInS/ZnS quantum dots for PET and optical imaging: improved radiochemical stability and controllable Cerenkov luminescence.

Publications

Intrinsically radioactive [64Cu]CuInS/ZnS quantum dots for PET and optical imaging: improved radiochemical stability and controllable Cerenkov luminescence.

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