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.