Preliminary study on SPECT/CT imaging of pancreatic cancer xenografts by targeting integrin α5 in pancreatic stellate cells.
Preliminary study on SPECT/CT imaging of pancreatic cancer xenografts by targeting integrin α5 in pancreatic stellate cells.
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DOI：
10.7150/jca.51190
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发表时间：
2021
影响因子：
3.9
通讯作者：
Zuo C
中科院分区：
文献类型：
--
作者：
Wang T;Peng Y;Li R;Li X;Zuo C
背景：整合素 α5 (ITGA5) 在胰腺癌基质中特异性过度表达，特别是在活化的胰腺星状细胞 (PSC) 中。通过靶向 PSC 进行胰腺癌的分子成像有其优势。目的：本研究旨在探讨以 PSC 为靶点的胰腺癌 ITGA5 靶向 SPECT/CT 成像的可行性。方法：通过蛋白质印迹和免疫荧光染色评估未经或经胰腺癌 SW1990 细胞条件培养基 (SW1990-CM) 处理的 PSC 中的 ITGA5 表达。采用 125I 放射性标记 ITGA5 特异性抑制剂 AV3 肽，合成 125I-AV3，并进一步研究标记率、体外稳定性和细胞摄取情况。将SW1990细胞单独或与PSCs分别注射到裸鼠左右下肢皮下，建立胰腺癌异种移植模型，然后对荷瘤裸鼠进行125I-AV3 SPECT/CT成像。通过免疫组织化学（IHC）染色检测肿瘤中ITGA5的表达。结果：125I-AV3具有优异的标记率和良好的体外稳定性。用 SW1990-CM 处理后，PSC 的 ITGA5 表达增加，125I-AV3 摄取增加。 SPECT/CT成像研究显示，125I-AV3主要积聚在右侧移植瘤（癌细胞和PSC共注射）中，而左侧移植瘤成像较差。此外，非放射性标记的AV3预处理后，两侧肿瘤对放射性示踪剂的摄取均受到显着抑制。 IHC染色显示SW1990+PSCs肿瘤的ITGA5阳性率高于SW1990肿瘤。结论：初步研究表明125I-AV3可通过靶向PSCs中的ITGA5用于胰腺癌的SPECT/CT成像，其与癌细胞的状态无关，可能具有特殊意义。
Background: Integrin α5 (ITGA5) is overexpressed specifically in pancreatic cancer stroma, specially, in the activated pancreatic stellate cells (PSCs). Molecular imaging of pancreatic cancer via targeting PSCs has its advantages. Purpose: This study aims to investigate the feasibility of ITGA5-targeted SPECT/CT imaging of pancreatic cancer by targeting PSCs. Methods: ITGA5 expression in PSCs treated without or with pancreatic cancer SW1990 cells conditioned medium (SW1990-CM) was assessed by western blotting and immunofluorescence staining. ITGA5 specific inhibitor AV3 peptide was radiolabeled with 125I to synthesize 125I-AV3, and the labeling rate, in vitro stability and cellular uptake were further investigated. SW1990 cells alone or with PSCs were injected subcutaneously on the left and right lower limbs of nude mice respectively to establish pancreatic cancer xenograft model, and then 125I-AV3 SPECT/CT imaging of pancreatic cancer-bearing nude mice was performed. The expression of ITGA5 in tumors was detected by immunohistochemical (IHC) staining. Results: 125I-AV3 has an excellent labeling rate and good in vitro stability. After treated with SW1990-CM, PSCs had an increased expression of ITGA5 and higher 125I-AV3 uptake. SPECT/CT imaging study showed that 125I-AV3 was mainly accumulated in the right xenografts (co-injection of cancer cells and PSCs), while the left xenografts tumors have a poor imaging. Moreover, the uptake of radiotracer in both side tumors was inhibited significantly after the non-radiolabeled AV3 pretreatment. IHC staining showed that SW1990 + PSCs tumor has a higher positive rate of ITGA5 than SW1990 tumor. Conclusion: The preliminary study suggests that 125I-AV3 can be used for SPECT/CT imaging of pancreatic cancer via targeting ITGA5 in PSCs, which is independent of the state of cancer cells and may have a special meaning.
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