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Published February 23, 2021 | Accepted Version + Supplemental Material
Journal Article Open

Integration of Multitargeted Polymer-Based Contrast Agents with Photoacoustic Computed Tomography: An Imaging Technique to Visualize Breast Cancer Intratumor Heterogeneity


One of the primary challenges in breast cancer diagnosis and treatment is intratumor heterogeneity (ITH), i.e., the coexistence of different genetically and epigenetically distinct malignant cells within the same tumor. Thus, the identification of ITH is critical for designing better treatments and hence to increase patient survival rates. Herein, we report a noninvasive hybrid imaging technology that integrates multitargeted and multiplexed patchy polymeric photoacoustic contrast agents (MTMPPPCAs) with single-impulse panoramic photoacoustic computed tomography (SIP-PACT). The target specificity ability of MTMPPPCAs to distinguish estrogen and progesterone receptor-positive breast tumors was demonstrated through both fluorescence and photoacoustic measurements and validated by tissue pathology analysis. This work provides the proof-of-concept of the MTMPPPCAs/SIP-PACT system to identify ITH in nonmetastatic tumors, with both high molecular specificity and real-time detection capability.

Additional Information

© 2021 American Chemical Society. Received: July 15, 2020; Accepted: January 14, 2021; Published: January 19, 2021. This research was supported by the National Institutes of Health, Center for Innovative Technology (CIT), and National Science Foundation (NSF)-I Corp program under Grants R15CA213093-01A1, MF17-020-LS, and 1756062 (all to C.S.M.). This work was sponsored by the NIH grants EB016986 (Pioneer Award), CA186567 (Transformative Research Award), NS090579, NS099717, and EB016963 (all to L.V.W.). Author Contributions. C.S.M. conceived the research idea and designed the research; C.S.M., L.L., and D.P. performed the research; C.S.M., L.L., and D.P. analyzed the data; C.S.M., L.L., D.P., and L.W. wrote the paper; G.P. and M.P. partially developed the organic synthesis of NH2-PEG-estrone; J.S. synthesized the squaraine (SQ650) dye; K.H. provided clinical inputs. The authors declare the following competing financial interest(s): In compliance with the George Mason University guidelines, C.S.M. discloses her financial interest in Nano-Guided Technologies, a biopharmaceutical developing nanoparticle technologies for medical applications. Nano-Guided Technologies did not support the aforementioned research, and this company has no rights to any technology or intellectual property developed as part of this research. L.V.W. has a financial interest in Microphotoacoustics, Inc., CalPACT, LLC, and Union Photoacoustic Technologies, Ltd., which, however, did not support this work. The other authors declare no competing financial interests.

Attached Files

Accepted Version - nihms-1691530.pdf

Supplemental Material - nn0c05893_si_001.pdf


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Additional details

August 20, 2023
October 23, 2023