Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA.
Department of Ultrasound, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People's Republic of China.
Mol Imaging Biol. 2020 Aug;22(4):1003-1011. doi: 10.1007/s11307-020-01478-9.
To explore the potential of B7-H3-targeted ultrasound molecular imaging (USMI) for longitudinal assessment and differentiation of metastatic and reactive sentinel lymph nodes (SLNs) in mouse models.
Metastatic and reactive SLN models were established by injection of 4T1 breast cancer cells and complete Freund's adjuvant (CFA) respectively to the 4th mammary fat pad of female BALB/c mice. At day 21, 28, and 35 after inoculation, USMI was performed following intravenous injection of B7-H3-targeted microbubbles (MB) or IgG-control microbubbles (MB). All SLNs were histopathologically examined after the last imaging session.
A total of 20 SLNs from tumor-bearing mice (T-SLNs) and five SLNs from CFA-injected mice (C-SLNs) were examined by USMI. Nine T-SLNs were histopathologically positive for metastasis (MT-SLNs). From day 21 to 35, T-SLNs showed a rising trend in MB signal with a steep increase in MT-SLNs at day 35 (213.5 ± 80.8 a.u.) as compared to day 28 (87.6 ± 77.2 a.u., P = 0.002) and day 21 (55.7 ± 35.5 a.u., P < 0.001). At day 35, MT-SLNs had significantly higher MB signal than non-metastatic T-SLNs (NMT-SLNs) (101.9 ± 48.0 a.u., P = 0.001) and C-SLNs (38.5 ± 34.0 a.u., P = 0.001); MB signal was significantly higher than MB in MT-SLNs (P = 0.001), but not in NMT-SLNs or C-SLNs (both P > 0.05). A significant correlation was detected between MB signal and volume fraction of metastasis in MT-SLNs (r = 0.76, P = 0.017).
B7-H3-targeted USMI allows differentiation of MT-SLNs from NMT-SLNs and C-SLNs in mouse models and has great potential to evaluate tumor burden in SLNs of breast cancer.
探索 B7-H3 靶向超声分子成像（USMI）用于评估和区分小鼠模型中转移性和反应性前哨淋巴结（SLN）的潜力。
通过向雌性 BALB/c 小鼠第 4 对乳腺脂肪垫内注射 4T1 乳腺癌细胞和完全弗氏佐剂（CFA），分别建立转移性和反应性 SLN 模型。接种后第 21、28 和 35 天，静脉注射 B7-H3 靶向微泡（MB）或 IgG 对照微泡（MB）后进行 USMI。最后一次成像后，所有 SLN 均进行组织病理学检查。
共对 20 个来自荷瘤小鼠的 SLN（T-SLNs）和 5 个来自 CFA 注射小鼠的 SLN（C-SLNs）进行了 USMI 检查。9 个 T-SLNs 组织病理学检查呈转移阳性（MT-SLNs）。从第 21 天到第 35 天，T-SLNs 的 MB 信号呈上升趋势，第 35 天 MT-SLNs 的 MB 信号急剧增加（213.5 ± 80.8 a.u.），与第 28 天（87.6 ± 77.2 a.u.，P = 0.002）和第 21 天（55.7 ± 35.5 a.u.，P < 0.001）相比。第 35 天，MT-SLNs 的 MB 信号明显高于非转移性 T-SLNs（NMT-SLNs）（101.9 ± 48.0 a.u.，P = 0.001）和 C-SLNs（38.5 ± 34.0 a.u.，P = 0.001）；MT-SLNs 的 MB 信号明显高于 MT-SLNs 的 MB 信号（P = 0.001），但在 NMT-SLNs 或 C-SLNs 中则没有（均 P > 0.05）。MT-SLNs 中 MB 信号与转移体积分数呈显著相关性（r = 0.76，P = 0.017）。
B7-H3 靶向 USMI 可区分小鼠模型中的 MT-SLNs、NMT-SLNs 和 C-SLNs，具有评估乳腺癌 SLN 肿瘤负荷的巨大潜力。
