Dataset Information

Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

ABSTRACT: Radiolabeling of molecules or nanoparticles to form imaging probes is critical for positron emission tomography (PET) imaging, which, with high sensitivity and the ability for quantitative imaging, has been widely used in the clinic. While conventional radiolabeling often employs chelator molecules, a general method for chelator-free radiolabeling of a wide range of materials remains to be developed. Herein, we determined that 10 different types of metal oxide (MxOy, M = Gd, Ti, Te, Eu, Ta, Er, Y, Yb, Ce, or Mo, x = 1-2, y = 2-5) nanomaterials with polyethylene glycol (PEG) modification could be labeled with 89Zr, a PET tracer, via a simple yet general chelator-free radiolabeling method upon simple mixing. High-labeling yields and good serum stabilities are achieved with this method, owing to the strong bonding between oxyphilic 89Zr4+ with oxygen atoms on the MxOy surface. Selecting 89Zr-Gd2O3-PEG as a multimodal imaging probe, we have successfully demonstrated in vivo PET imaging of draining lymph nodes, which are also visualized under magnetic resonance imaging, showing advantages over free 89Zr in the mapping of draining lymph node networks. Our work describes a general and simple method for chelator-free radiolabeling of metal oxide nanostructures, which is promising for the development of multifunctional nanoprobes in biomedical imaging.

SUBMITTER: Cheng L

PROVIDER: S-EPMC5752591 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

Cheng Liang L Shen Sida S Jiang Dawei D Jin Qiutong Q Ellison Paul A PA Ehlerding Emily B EB Goel Shreya S Song Guosheng G Huang Peng P Barnhart Todd E TE Liu Zhuang Z Cai Weibo W

ACS nano 20171129 12

Radiolabeling of molecules or nanoparticles to form imaging probes is critical for positron emission tomography (PET) imaging, which, with high sensitivity and the ability for quantitative imaging, has been widely used in the clinic. While conventional radiolabeling often employs chelator molecules, a general method for chelator-free radiolabeling of a wide range of materials remains to be developed. Herein, we determined that 10 different types of metal oxide (M<sub>x</sub>O<sub>y,</sub> M = Gd ...[more]

PMID: 29178789

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Project description:Selection of the right drug for the right patient is a promising approach to increase clinical benefit of targeted therapy with monoclonal antibodies (mAbs). Assessment of in vivo biodistribution and tumor targeting of mAbs to predict toxicity and efficacy is expected to guide individualized treatment and drug development. Molecular imaging with positron emission tomography (PET) using zirconium-89 ((89)Zr)-labeled monoclonal antibodies also known as (89)Zr-immuno-PET, visualizes and quantifies uptake of radiolabeled mAbs. This technique provides a potential imaging biomarker to assess target expression, as well as tumor targeting of mAbs. In this review we summarize results from initial clinical trials with (89)Zr-immuno-PET in oncology and discuss technical aspects of trial design. In clinical trials with (89)Zr-immuno-PET two requirements should be met for each (89)Zr-labeled mAb to realize its full potential. One requirement is that the biodistribution of the (89)Zr-labeled mAb (imaging dose) reflects the biodistribution of the drug during treatment (therapeutic dose). Another requirement is that tumor uptake of (89)Zr-mAb on PET is primarily driven by specific, antigen-mediated, tumor targeting. Initial trials have contributed toward the development of (89)Zr-immuno-PET as an imaging biomarker by showing correlation between uptake of (89)Zr-labeled mAbs on PET and target expression levels in biopsies. These results indicate that (89)Zr-immuno-PET reflects specific, antigen-mediated binding. (89)Zr-immuno-PET was shown to predict toxicity of RIT, but thus far results indicating that toxicity of mAbs or mAb-drug conjugate treatment can be predicted are lacking. So far, one study has shown that molecular imaging combined with early response assessment is able to predict response to treatment with the antibody-drug conjugate trastuzumab-emtansine, in patients with human epithelial growth factor-2 (HER2)-positive breast cancer. Future studies would benefit from a standardized criterion to define positive tumor uptake, possibly supported by quantitative analysis, and validated by linking imaging data with corresponding clinical outcome. Taken together, these results encourage further studies to develop (89)Zr-immuno-PET as a predictive imaging biomarker to guide individualized treatment, as well as for potential application in drug development.

Dataset Information

Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

Publications

Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

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