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Simultaneous Detection of Multiple Tumor-targeted Gold Nanoparticles in HER2-Positive Breast Tumors Using
Abhilash Samykutty1, Karl N Thomas1, Molly McNally1
1From the Department of Surgery, Stephenson Comprehensive Cancer Center, University of Oklahoma, Oklahoma City, Okla (A.S., M.M., J.H., L.M., J.C.C.S.); Department of Radiation Oncology, University of Oklahoma Health Science Center, Oklahoma City, Okla (C.H.); Atrium Wake Forest Health Comprehensive Cancer Center, Winston-Salem, NC (A.T., L.M.); Department of Surgery, Duke University, Durham, NC (A.C.); Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27013 (A.S., K.N.T., M.M., L.R.M.); Department of Mechanical Engineering, Virginia Tech University, Blacksburg, Va (B.B., Y.Z., M.C.T.); and Department of Epidemiology and Biostatistics (T.G., Z.S.) and Department of Pathology (W.E.G.), University of Alabama at Birmingham, Birmingham, Ala.
Abstract:
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.
