HER3 PET Imaging Predicts Response to Pan Receptor Tyrosine Kinase Inhibition Therapy in Gastric Cancer.
HER3 PET Imaging Predicts Response to Pan Receptor Tyrosine Kinase Inhibition Therapy in Gastric Cancer.
复制标题
HER3 PET成像可以预测胃癌中对PAN受体酪氨酸激酶抑制疗法的反应。
DOI：
10.1007/s11307-022-01763-9
复制
发表时间：
2023-04
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
新一代受体酪氨酸激酶抑制剂（RTKI）已被证明可以提高许多实体瘤的生存率。然而，需要成像生物标志物来选择患者和预测治疗反应。本研究评估了 68 Ga-NOTA-HER3P1 PET/MRI 上 HER3 定量变化的用途，用于预测胃癌 (GCa) 中泛 RTKI 的早期反应。评估 GCa 细胞系的 RTK 表达和下游信号通路（AKT 和 MAPK）。用 0.01-1 μmol/L 阿法替尼（一种泛 RTKI）处理 24-72 小时后评估细胞活力。选择表达HER3的阿法替尼敏感细胞（NCI-N87）和耐药细胞（SNU16）用于评估RTK表达和下游通路的变化，用0.1 μmol/L阿法替尼治疗24-72小时。在基线和阿法替尼治疗（10 mg/kg，口服，每日）后 4 天，对皮下 NCI-N87 和 SNU16 异种移植物（nu:nu，n = 12/组）进行 68 Ga-NOTA-HER3P1 PET/MRI。 PET 测量值的时间变化与肿瘤中 HER3 表达、肿瘤生长速率和治疗反应相关。使用阿法替尼治疗后，NCI-N87细胞在72小时内表现出总HER3表达增加，并且其他RTK和下游节点减少，而SNU16细胞表现出总HER3和下游节点没有显着变化。 68 Ga-HER3P1 PET/MRI 显示 NCI-N87 中的摄取增加，而 SNU16 肿瘤中没有显着变化（第 4 天与基线 SUV 平均值相比：NCI-N87 中为 3.8 ± 0.7 与 1.6 ± 0.6，p < 0.05；SNU16 中为 1.5 ± 0.7 与 1.7 ± 0.7，p > 0.05）。这些结果与组织病理学分析中的 HER3 表达和治疗 3 周内的肿瘤生长一致（治疗组与对照组的平均肿瘤体积：NCI-N87 中为 11 ± 17 mm3 与 293 ± 79 mm3，p < 0.001；SNU16 中为 238 ± 91 mm3 与 282 ± 35 mm3，p > 0.05）。 HER3 PET 的定量变化可用于预测治疗开始后几天内对泛 RTKI 的反应，并有助于个性化 GCa 管理。
New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa). GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24–72 h of treatment with 0.01–1 μmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24–72 h of 0.1 μmol/L afatinib treatment. 68 Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response. With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68 Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUVmean: 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm3 vs. 293 ± 79 mm3, p < 0.001 in NCI-N87, and 238 ± 91 mm3 vs. 282 ± 35 mm3, p > 0.05 in SNU16). Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management.
登录
查看更多内容
影响因子：
28.2
作者：
Montero-Conde C;Ruiz-Llorente S;Dominguez JM;Knauf JA;Viale A;Sherman EJ;Ryder M;Ghossein RA;Rosen N;Fagin JA
通讯作者：
Fagin JA
影响因子：
64.8
作者：
Sergina, Natalia V.;Rausch, Megan;Wang, Donghui;Blair, Jimmy;Hann, Byron;Shokat, Kevan M.;Moasser, Mark M.
通讯作者：
Moasser, Mark M.
影响因子：
3.7
作者：
Cao GD;Chen K;Xiong MM;Chen B
通讯作者：
Chen B
影响因子：
1.6
作者：
Leece, Alicia K.;Heidari, Pedram;Mahmood, Umar
通讯作者：
Mahmood, Umar
影响因子：
11.5
作者：
Leto, Simonetta M.;Sassi, Francesco;Trusolino, Livio
通讯作者：
Trusolino, Livio