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In vivo Biodistribution of Radiolabeled Acoustic Protein Nanostructures

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Abstract

Purpose

Contrast-enhanced ultrasound plays an expanding role in oncology, but its applicability to molecular imaging is hindered by a lack of nanoscale contrast agents that can reach targets outside the vasculature. Gas vesicles (GVs)—a unique class of gas-filled protein nanostructures—have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting. The purpose of the present study is to determine the quantitative biodistribution of GVs, which is critical for their development as imaging agents.

Procedures

We use a novel bioorthogonal radiolabeling strategy to prepare technetium-99m-radiolabeled ([99mTc])GVs in high radiochemical purity. We use single photon emission computed tomography (SPECT) and tissue counting to quantitatively assess GV biodistribution in mice.

Results

Twenty minutes following administration to mice, the SPECT biodistribution shows that 84 % of [99mTc]GVs are taken up by the reticuloendothelial system (RES) and 13 % are found in the gall bladder and duodenum. Quantitative tissue counting shows that the uptake (mean ± SEM % of injected dose/organ) is 0.6 ± 0.2 for the gall bladder, 46.2 ± 3.1 for the liver, 1.91 ± 0.16 for the lungs, and 1.3 ± 0.3 for the spleen. Fluorescence imaging confirmed the presence of GVs in RES.

Conclusions

These results provide essential information for the development of GVs as targeted nanoscale imaging agents for ultrasound.

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Funding

JLF, MY, AF, MS, and SF acknowledge the financial support of the National Institutes of Health (NIH 1R01EB018975) and the Canadian Institutes for Health Research (CIHR MOP136842). AZ, HB, NJ, and JV acknowledge the financial support of Canadian Cancer Society (Innovation grant 2015:703857) and the Canadian Institutes for Health Research (CIHR/NSERC CHRP Grant 2016: 493840-16).

Author information

Author notes

  1. Johann Le Floc’h and Aimen Zlitni contributed equally to this work.

Authors and Affiliations

  1. Sunnybrook Research Institute, 2075 Bayview Avenue, Room S640, Toronto, ON, M4N 3M5, Canada

    Johann Le Floc’h, Melissa Yin & F. Stuart Foster

  2. Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada

    Aimen Zlitni, Holly A. Bilton, Nancy R. Janzen & John F. Valliant

  3. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA

    Arash Farhadi & Mikhail G. Shapiro

Authors
  1. Johann Le Floc’h
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  2. Aimen Zlitni
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  3. Holly A. Bilton
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  4. Melissa Yin
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Corresponding authors

Correspondence to Johann Le Floc’h or John F. Valliant.

Ethics declarations

All experimental procedures were approved by the Animal Care Committees at Sunnybrook Research Institute and McMaster University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Le Floc’h, J., Zlitni, A., Bilton, H.A. et al. In vivo Biodistribution of Radiolabeled Acoustic Protein Nanostructures. Mol Imaging Biol 20, 230–239 (2018). https://doi.org/10.1007/s11307-017-1122-6

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