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Molecular Imaging Using Light-Absorbing Imaging Agents and a Clinical Optical Breast Imaging System—a Phantom Study

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Abstract

Purpose

The aim of the study was to determine the feasibility of using a clinical optical breast scanner with molecular imaging strategies based on modulating light transmission.

Procedures

Different concentrations of single-walled carbon nanotubes (SWNT; 0.8–20.0 nM) and black hole quencher-3 (BHQ-3; 2.0–32.0 µM) were studied in specifically designed phantoms (200–1,570 mm3) with a clinical optical breast scanner using four wavelengths. Each phantom was placed in the scanner tank filled with optical matching medium. Background scans were compared to absorption scans, and reproducibility was assessed.

Results

All SWNT phantoms were detected at four wavelengths, with best results at 684 nm. Higher concentrations (≥8.0 µM) were needed for BHQ-3 detection, with the largest contrast at 684 nm. The optical absorption signal was dependent on phantom size and concentration. Reproducibility was excellent (intraclass correlation 0.93–0.98).

Conclusion

Nanomolar concentrations of SWNT and micromolar concentrations of BHQ-3 in phantoms were reproducibly detected, showing the potential of light absorbers, with appropriate targeting ligands, as molecular imaging agents for clinical optical breast imaging.

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Acknowledgments

This work was supported, in part, by funding from ART Advanced Research Technologies Inc., National Cancer Institute (NCI) In Vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747 (SSG), NCI Center of Cancer Nanotechnology Excellence (CCNE) CA119367 U54, and the Canary Foundation. We also thank Adam de la Zerda for helpful discussions.

Author information

Authors and Affiliations

  1. Department of Radiology, Stanford University Medical Center, Stanford, CA, USA

    Stephanie M. W. Y. van de Ven, Debra M. Ikeda & Sanjiv S. Gambhir

  2. Molecular Imaging Program at Stanford (MIPS), Stanford University Medical Center, Stanford, CA, USA

    Stephanie M. W. Y. van de Ven & Sanjiv S. Gambhir

  3. ART Advanced Research Technologies Inc., Montreal, QC, Canada

    Niculae Mincu, Jean Brunette, Guobin Ma & Mario Khayat

  4. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Sanjiv S. Gambhir

  5. Molecular Imaging Program at Stanford, The James H Clark Center, 318 Campus Drive; East Wing, 1st Floor, Stanford, CA, 94305-5427, USA

    Sanjiv S. Gambhir

Authors
  1. Stephanie M. W. Y. van de Ven
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  2. Niculae Mincu
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  3. Jean Brunette
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  4. Guobin Ma
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  5. Mario Khayat
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  6. Debra M. Ikeda
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  7. Sanjiv S. Gambhir
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Corresponding author

Correspondence to Sanjiv S. Gambhir.

Electronic supplementary materials

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Supp. Fig. 1

Average absorption measurements at 732 nm of phantoms of three sizes (200, 780, and 1,570 mm3) containing six concentrations of SWNTs (0.8, 1.6, 2.4, 4, 6.4, and 20 nM). Error bars represent the standard deviation of duplicate measurements. (GIF 19 kb)

High Resolution (TIFF 305 kb)

Supp. Fig. 2

Average absorption measurements at 781 nm of phantoms of three sizes (200, 780, and 1,570 mm3) containing six concentrations of SWNTs (0.8, 1.6, 2.4, 4, 6.4, and 20 nM). Error bars represent the standard deviation of duplicate measurements. (GIF 27 kb)

High Resolution (TIFF 320 kb)

Supp. Fig. 3

Average absorption measurements at 827 nm of phantoms of three sizes (200, 780, and 1,570 mm3) containing six concentrations of SWNTs (0.8, 1.6, 2.4, 4, 6.4, and 20 nM). Error bars represent the standard deviation of duplicate measurements. (GIF 29 kb)

High Resolution (TIFF 304 kb)

Supp. Fig. 4

Average absorption measurements at 732 nm of phantoms of two sizes (200 and 780 mm3) containing five concentrations of BHQ-3 (2.0, 4.0, 8.0, 16, and 32 µM). Error bars represent the standard deviation of duplicate measurements. (GIF 26 kb)

High Resolution (TIFF 234 kb)

Supp. Fig. 5

Average absorption measurements at 781 nm of phantoms of two sizes (200 and 780 mm3) containing five concentrations of BHQ-3 (2.0, 4.0, 8.0, 16, and 32 µM). Error bars represent the standard deviation of duplicate measurements. (GIF 20 kb)

High Resolution (TIFF 228 kb)

Supp. Fig. 6

Average absorption measurements at 827 nm of phantoms of two sizes (200 and 780 mm3) containing five concentrations of BHQ-3 (2.0, 4.0, 8.0, 16, and 32 µM). Error bars represent the standard deviation of duplicate measurements. (GIF 20 kb)

High Resolution (TIFF 229 kb)

Supp. Table 1

Dependency of optical absorption signal (y) on SWNT/BHQ-3 concentration (x) for each phantom size and wavelength. (RTF 32 kb)

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van de Ven, S.M.W.Y., Mincu, N., Brunette, J. et al. Molecular Imaging Using Light-Absorbing Imaging Agents and a Clinical Optical Breast Imaging System—a Phantom Study. Mol Imaging Biol 13, 232–238 (2011). https://doi.org/10.1007/s11307-010-0356-3

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