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Molecular Imaging and Biology

, Volume 20, Issue 2, pp 230–239 | Cite as

In vivo Biodistribution of Radiolabeled Acoustic Protein Nanostructures

  • Johann Le Floc’h
  • Aimen Zlitni
  • Holly A. Bilton
  • Melissa Yin
  • Arash Farhadi
  • Nancy R. Janzen
  • Mikhail G. Shapiro
  • John F. Valliant
  • F. Stuart Foster
Research Article

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.

Key Words

Ultrasound contrast agent Acoustic nanostructures Gas vesicles Biodistribution SPECT/CT Bioorthogonal chemistry Technetium-99m 

Notes

Funding Information

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).

Compliance with Ethical Standards

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.

Supplementary material

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Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  1. 1.Sunnybrook Research InstituteTorontoCanada
  2. 2.Department of Chemistry and Chemical BiologyMcMaster UniversityHamiltonCanada
  3. 3.Division of Chemistry and Chemical EngineeringCalifornia Institute of TechnologyPasadenaUSA

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