Johann Le Floc'h1, Aimen Zlitni2, Holly A Bilton2, Melissa Yin3, Arash Farhadi4, Nancy R Janzen2, Mikhail G Shapiro4, John F Valliant5, F Stuart Foster3. 1. Sunnybrook Research Institute, 2075 Bayview Avenue, Room S640, Toronto, ON, M4N 3M5, Canada. jlefloch@sri.utoronto.ca. 2. Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada. 3. Sunnybrook Research Institute, 2075 Bayview Avenue, Room S640, Toronto, ON, M4N 3M5, Canada. 4. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. 5. Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada. valliant@mcmaster.ca.
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.
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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