Overexpression of tissue factor (TF) has been associated with increased tumor growth, tumor angiogenesis, and metastatic potential in many malignancies, including pancreatic cancer. Additionally, high TF expression was shown to strongly correlate with poor prognoses and decreased survival in pancreatic cancer patients. Herein, we exploited the potential targeting of TF for positron emission tomography (PET) imaging of pancreatic cancer. The TF-targeted tracer was developed through radiolabeling of the anti-human TF monoclonal antibody (ALT-836) with ⁸⁹Zr. The tracer was characterized by fluorescence microscopy and flow cytometry assays in BXPC-3 and PANC-1 cells, two pancreatic cancer cell lines with high and low TF expression levels, respectively. Non-invasive PET scans were acquired in tumor-bearing mice injected with ⁸⁹Zr-Df-ALT-836. Additionally, ex vivo biodistribution, blocking, and histological studies were performed to establish the affinity and specificity of ⁸⁹Zr-Df-ALT-836 for TF in vivo. ⁸⁹Zr-labeling of Df-ALT-836 was achieved in high yield and good specific activity. Flow cytometry and microscopy studies revealed no detectable difference in TF-binding affinity between ALT-836 and Df-ALT-836 in vitro. Longitudinal PET scans unveiled a lasting and prominent ⁸⁹Zr-Df-ALT-836 uptake in BXPC-3 tumors (peak at 31.5 ± 6.0%ID/g at 48 h post-injection; n = 3), which was significantly abrogated (2.3 ± 0.5%ID/g at 48 h post-injection; n = 3) when mice were pre-injected with a blocking dose (50 mg/kg) of unlabeled ALT-836. Ex vivo biodistribution data confirmed the accuracy of the PET results, and histological analysis correlated high tumor uptake with in situ TF expression. Taken together, these results attest to the excellent affinity and TF-specificity of ⁸⁹Zr-Df-ALT-836. With elevated, persistent, and specific accumulation in TF-positive BXPC-3 tumors, PET imaging using ⁸⁹Zr-Df-ALT-836 promises to open new avenues for improving future diagnosis, stratification, and treatment response assessment in pancreatic cancer patients.

组织因子（TF）的过度表达与包括胰腺癌在内的许多恶性肿瘤的肿瘤生长，肿瘤血管生成和转移潜力有关。此外，显示高TF表达与胰腺癌患者的不良预后和降低的生存率密切相关。本文中，我们利用TF的潜在靶点用于胰腺癌的正电子发射断层扫描（PET）成像。通过以⁸⁹锆 通过荧光显微镜和流式细胞仪检测，在两种分别具有高和低TF表达水平的胰腺癌细胞系BXPC-3和PANC-1中对示踪剂进行了表征。在注射了⁸⁹ Zr-Df-ALT-836的荷瘤小鼠中进行了非侵入性PET扫描。此外，进行了离体生物分布，阻断和组织学研究，以建立⁸⁹ Zr-Df-ALT-836对TF体内的亲和力和特异性。Df-ALT-836的⁸⁹ Zr标记实现了高收率和良好的比活。流式细胞仪和显微镜研究表明，ALT-836和Df-ALT-836在体外的TF结合亲和力没有可检测的差异。纵向PET扫描揭示了BXPC-3肿瘤持久且显着的⁸⁹ Zr-Df-ALT-836吸收（注射后48 h峰值为31.5±6.0％ID / g； n = 3），该值被显着消除（2.3）注射后48 h，±0.5％ID / g； n = 3），当小鼠预先注射阻断剂量（50 mg / kg）的未标记ALT-836。离体的生物分布数据证实了PET结果的准确性，并且组织学分析将高肿瘤摄取与原位TF表达相关。综上所述，这些结果证明了⁸⁹ Zr-Df-ALT-836具有出色的亲和力和TF特异性。在TF阳性BXPC-3肿瘤中出现高水平，持续性和特异性积累，PET成像使用⁸⁹Zr-Df-ALT-836有望为改善胰腺癌患者的未来诊断，分层和治疗反应评估开辟新途径。