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Published February 25, 2010 | Published
Book Section - Chapter Open

Fabricating multifunctional microbubbles and nanobubbles for concurrent ultrasound and photoacoustic imaging


Background: Clinical ultrasound (US) uses ultrasonic scattering contrast to characterize subcutaneous anatomic structures. Photoacoustic (PA) imaging detects the functional properties of thick biological tissue with high optical contrast. In the case of image-guided cancer ablation therapy, simultaneous US and PA imaging can be useful for intraoperative assessment of tumor boundaries and ablation margins. In this regard, accurate co-registration between imaging modalities and high sensitivity to cancer cells are important. Methods: We synthesized poly-lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) encapsulating India ink or indocyanine green (ICG). Multiple tumor simulators were fabricated by entrapping ink MBs or NBs at various concentrations in gelatin phantoms for simultaneous US and PA imaging. MBs and NBs were also conjugated with CC49 antibody to target TAG-72, a human glycoprotein complex expressed in many epithelial-derived cancers. Results: Accurate co-registration and intensity correlation were observed in US and PA images of MB and NB tumor simulators. MBs and NBs conjugating with CC49 effectively bound with over-expressed TAG-72 in LS174T colon cancer cell cultures. ICG was also encapsulated in MBs and NBs for the potential to integrate US, PA, and fluorescence imaging. Conclusions: Multifunctional MBs and NBs can be potentially used as a general contrast agent for multimodal intraoperative imaging of tumor boundaries and therapeutic margins.

Additional Information

© 2010 Society of Photo-Optical Instrumentation Engineers (SPIE). This work was supported in part by grants from the National Institutes of Health (R01 EB000712, R01 EB008085, and U54 CA136398 — the Network for Translational Research — to L.V.W.) and the Department of Defense Breast Cancer Research Program (W81XWH-07 to R. X.). L.V.W. has a financial interest in Microphotoacoustics, Inc. and in Endra, Inc., which, however, did not support this work.

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