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Med. Phys. 37, 4193 (2010); doi:10.1118/1.3466696 (8 pages)

Thermoacoustic molecular tomography with magnetic nanoparticle contrast agents for targeted tumor detection

Liming Nie, Zhongmin Ou, Sihua Yang, and Da Xing

MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou 510631, China and College of Biophotonics, South China Normal University, Guangzhou 510631, China

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(Received 13 November 2009; accepted 30 June 2010; revised 30 June 2010; published online 21 July 2010)

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Purpose: The primary feasibility steps of demonstrating the ability of microwave-induced thermoacoustic (TA) in phantoms have been previously reported. However, none were shown to target a diseased site in living subjects in thermoacoustic tomography (TAT) field so far. To determine the expressions of oncogenic surface molecules, it is quite necessary to image tumor lesions and acquire pathogenic status on them via TAT.
Methods: Compared to biological tissues, iron oxide nanoparticles have a much higher microwave absorbance. Fe3O4/polyaniline (PANI) nanoparticles were prepared via polymerization of aniline in the Fe3O4 superparamagnetic fluids. Then Fe3O4/PANI was conjugated to folic acid (FA), which can bind specifically to the surface of the folate receptor used as a tumor marker. FA-Fe3O4/PANI targeted tumor was irradiated by pulsed microwave at 6 GHz for thermoacoustic detection and imaging.
Results: The effect of the Fe3O4/PANI superparamagnetic nanoparticles for enhancing TAT images was successfully investigated in ex vivo human blood and in vivo mouse tail. Intravenous administration of the targeted nanoparticles to mice bearing tumors showed fivefold greater thermoacoustic signal and much longer elimination time than that of mice injected with nontargeted nanoparticles in the tumor. The specific targeting ability of FA-Fe3O4/PANI to tumor was also verified on fluorescence microscopy.
Conclusions: Fabricated iron oxide nanoparticles conjugated with tumor ligands for targeted TAT tumor detection at the molecular level was reported for the first time. The results indicate that thermoacoustic molecular imaging with functionalized iron oxide nanoparticles may contribute to targeted and functional early cancer imaging. Also, the modified iron oxide nanoparticles combined with suitable tumor markers may also be used as novel nanomaterials for targeted and guided cancer thermal therapy.

© 2010 American Association of Physicists in Medicine

ACKNOWLEDGMENTS

This research was supported by the National Basic Research Program of China (Grant No. 2010CB732602), the Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT0829), the National Natural Science Foundation of China (Grant Nos. 30627003, 30870676, and 30800261), the Natural Science Foundation of Guangdong Province (Grant No. 7117865), and the Scientific Research Foundation of the State Human Resource Ministry for Returned Chinese Scholars (2008). The authors also acknowledge Professor Donglin Zhao for the supply of Fe3O4/PANI nanoparticles and Dr. Feifan Zhou for the helpful discussion.

Article Outline

  1. INTRODUCTION
  2. MATERIALS AND METHODS
    1. Chemicals and reagents
    2. FA-Fe3O4 /PANI synthesis
    3. Cell lines and the animal model
    4. Fluorescence microscopy of targeted Fe3O4 /PANI
    5. Data acquisition system and imaging reconstruction
  3. RESULTS
    1. Functionalized iron oxide nanoparticles for TAT molecular imaging
    2. In vivo TA imaging of Fe3O4 /PANIs in mouse tail
    3. TAT molecular imaging with selective targeting on tumor model
    4. Fluorescence verification of FA-Fe3O4 /PANI targeting ability
  4. CONCLUSION AND DISCUSSION

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