Simultaneous Detection of Multiple Tumor-targeted Gold Nanoparticles in HER2-Positive Breast Tumors Using Optoacoustic Imaging.

Purpose To develop optoacoustic, spectrally distinct, actively targeted gold nanoparticle-based near-infrared probes (trastuzumab [TRA], TRA-Aurelia-1, and TRA-Aurelia-2) that can be individually identifiable at multispectral optoacoustic tomography (MSOT) of human epidermal growth factor receptor 2 (HER2)-positive breast tumors. Materials and Methods Gold nanoparticle-based near-infrared probes (Aurelia-1 and 2) that are optoacoustically active and spectrally distinct for simultaneous MSOT imaging were synthesized and conjugated to TRA to produce TRA-Aurelia-1 and 2. Freshly resected human HER2-positive (n = 6) and HER2-negative (n = 6) triple-negative breast cancer tumors were treated with TRA-Aurelia-1 and TRA-Aurelia-2 for 2 hours and imaged with MSOT. HER2-expressing DY36T2Q cells and HER2-negative MDA-MB-231 cells were implanted orthotopically into mice (n = 5). MSOT imaging was performed 6 hours following the injection, and the Friedman test was used for analysis. Results TRA-Aurelia-1 (absorption peak, 780 nm) and TRA-Aurelia-2 (absorption peak, 720 nm) were spectrally distinct. HER2-positive human breast tumors exhibited a significant increase in optoacoustic signal following TRA-Aurelia-1 (28.8-fold) or 2 (29.5-fold) (P = .002) treatment relative to HER2-negative tumors. Treatment with TRA-Aurelia-1 and 2 increased optoacoustic signals in DY36T2Q tumors relative to those in MDA-MB-231 controls (14.8-fold, P < .001; 20.8-fold, P < .001, respectively). Conclusion The study demonstrates that TRA-Aurelia 1 and 2 nanoparticles operate as a spectrally distinct HER2 breast tumor-targeted in vivo optoacoustic agent. Keywords: Molecular Imaging, Nanoparticles, Photoacoustic Imaging, Breast Cancer Supplemental material is available for this article. © RSNA, 2023.

The Interplay of Biomechanical and Biological Changes Following Meniscus Injury.

PURPOSE OF REVIEW: Meniscus injury often leads to joint degeneration and post-traumatic osteoarthritis (PTOA) development. Therefore, the purpose of this review is to outline the current understanding of biomechanical and biological repercussions following meniscus injury and how these changes impact meniscus repair and PTOA development. Moreover, we identify key gaps in knowledge that must be further investigated to improve meniscus healing and prevent PTOA. RECENT FINDINGS: Following meniscus injury, both biomechanical and biological alterations frequently occur in multiple tissues in the joint. Biomechanically, meniscus tears compromise the ability of the meniscus to transfer load in the joint, making the cartilage more vulnerable to increased strain. Biologically, the post-injury environment is often characterized by an increase in pro-inflammatory cytokines, catabolic enzymes, and immune cells. These multi-faceted changes have a significant interplay and result in an environment that opposes tissue repair and contributes to PTOA development. Additionally, degenerative changes associated with OA may cause a feedback cycle, negatively impacting the healing capacity of the meniscus. Strides have been made towards understanding post-injury biological and biomechanical changes in the joint, their interplay, and how they affect healing and PTOA development. However, in order to improve clinical treatments to promote meniscus healing and prevent PTOA development, there is an urgent need to understand the physiologic changes in the joint following injury. In particular, work is needed on the in vivo characterization of the temporal biomechanical and biological changes that occur in patients following meniscus injury and how these changes contribute to PTOA development.