From 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.
Radiol Imaging Cancer. 2023 May;5(3):e220180. doi: 10.1148/rycan.220180.
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 ( = 6) and HER2-negative ( = 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 ( = 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) ( = .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, < .001; 20.8-fold, < .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. Molecular Imaging, Nanoparticles, Photoacoustic Imaging, Breast Cancer © RSNA, 2023.
目的 开发光声、光谱上有区别的、主动靶向的金纳米粒子近红外探针（曲妥珠单抗[TRA]、TRA-Aurelia-1 和 TRA-Aurelia-2），使其能够在人表皮生长因子受体 2（HER2）阳性乳腺癌的多光谱光声断层扫描（MSOT）中进行单独识别。 材料与方法 合成光声活性和光谱上有区别的金纳米粒子近红外探针（Aurelia-1 和 2），用于同时进行 MSOT 成像，并将其与 TRA 缀合以产生 TRA-Aurelia-1 和 2。新鲜切除的人 HER2 阳性（=6）和 HER2 阴性（=6）三阴性乳腺癌肿瘤用 TRA-Aurelia-1 和 TRA-Aurelia-2 处理 2 小时，并用 MSOT 成像。将表达 HER2 的 DY36T2Q 细胞和 HER2 阴性的 MDA-MB-231 细胞原位植入小鼠（=5）。注射后 6 小时进行 MSOT 成像，并用 Friedman 检验进行分析。 结果 TRA-Aurelia-1（吸收峰，780nm）和 TRA-Aurelia-2（吸收峰，720nm）光谱有区别。与 HER2 阴性肿瘤相比，TRA-Aurelia-1（28.8 倍）或 2（29.5 倍）处理后，HER2 阳性人乳腺癌肿瘤的光声信号显著增加（=0.002）。与 MDA-MB-231 对照相比，DY36T2Q 肿瘤用 TRA-Aurelia-1 和 2 处理后光声信号增加（14.8 倍，<0.001；20.8 倍，<0.001）。 结论 本研究表明，TRA-Aurelia 1 和 2 纳米粒子作为一种光谱上有区别的 HER2 乳腺癌肿瘤靶向体内光声造影剂。 分子影像学、纳米粒子、光声成像、乳腺癌 ©RSNA，2023 年。
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