Huang Wenpeng, Chao Fangfang, Hsu Jessica C, Sun Xinyao, Barnhart Todd E, Engle Jonathan W, Han Xingmin, Kang Lei, Cai Weibo
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
Departments of Radiology and Medical Physics, University of Wisconsin - Madison, Madison, WI 53705, USA.
Colloids Surf A Physicochem Eng Asp. 2025 Oct 20;723. doi: 10.1016/j.colsurfa.2025.137332. Epub 2025 May 29.
ImmunoPET imaging of PD-L1 has emerged as a promising strategy for patient stratification and treatment response monitoring in immunotherapy. This study aimed to evaluate [Zr]Zr-DFO-Durvalumab in noninvasive imaging of PD-L1 expression in non-small cell lung cancer (NSCLC) and bladder cancer.
Durvalumab was conjugated with -SCN-Bn-DFO and labeled with [Zr]Zr-oxalate, achieving high radiochemical purity (> 99 %) and stability. PD-L1 expression in human NSCLC (H1975, A549) and bladder cancer (HT1376, T24) cell lines was characterized via flow cytometry and immunofluorescence. binding and uptake studies were conducted to assess specificity. ImmunoPET imaging and biodistribution analyses were performed in mouse xenograft models. Additionally, fluorescence-guided imaging using IRDye 800CW-labeled Durvalumab was evaluated.
H1975 and HT1376 cells exhibited strong PD-L1 expression and high tracer uptake, while A549 and T24 cells were low in PD-L1 expression. PET imaging revealed significantly higher uptake in PD-L1-positive tumors. At 48 h p.i., the accumulation in H1975 tumor was 10.73 ± 1.89 %ID/g, compared to 4.47 ± 0.55 %ID/g in A549 tumor ( = 0.0219) and 4.60 ± 0.46 %ID/g in blocking control ( = 0.0228). HT1376 tumor reached 10.63 ± 1.35 %ID/g, significantly higher than T24 (4.10 ± 0.89 %ID/g, = 0.0037), blocking (4.10 ± 0.92 %ID/g, = 0.0036), and [Zr]Zr-DFO-IgG control (5.67 ± 0.90 %ID/g, = 0.0089). Tumor-to-muscle ratios at 48 h for H1975 and HT1376 tumors were 14.30 ± 2.02 and 15.00 ± 1.62, respectively, indicating excellent contrast. Fluorescence imaging with IRDye 800CW-Durvalumab further confirmed the uptake in PD-L1-specific tumors. No significant histological abnormalities were observed in major organs. The estimated human effective dose was 0.0522 mSv/MBq.
[Zr]Zr-DFO-Durvalumab enables specific, high-contrast ImmunoPET and fluorescence imaging of PD-L1-expressing NSCLC and bladder cancers. This dual-modality imaging platform holds potential for noninvasive assessment of PD-L1 status and personalized immunotherapy planning.
PD-L1的免疫正电子发射断层扫描（ImmunoPET）成像已成为免疫治疗中患者分层和治疗反应监测的一种有前景的策略。本研究旨在评估[Zr]Zr-DFO-度伐利尤单抗在非小细胞肺癌（NSCLC）和膀胱癌中对PD-L1表达的无创成像。
度伐利尤单抗与-SCN-Bn-DFO偶联，并用[Zr]Zr-草酸盐标记，获得了高放射化学纯度（>99%）和稳定性。通过流式细胞术和免疫荧光对人NSCLC（H1975、A549）和膀胱癌（HT1376、T24）细胞系中的PD-L1表达进行了表征。进行结合和摄取研究以评估特异性。在小鼠异种移植模型中进行了免疫正电子发射断层扫描成像和生物分布分析。此外，还评估了使用IRDye 800CW标记的度伐利尤单抗进行的荧光引导成像。
H1975和HT1376细胞表现出强烈的PD-L1表达和高示踪剂摄取，而A549和T24细胞的PD-L1表达较低。正电子发射断层扫描成像显示PD-L1阳性肿瘤中的摄取明显更高。注射后48小时，H1975肿瘤中的蓄积为10.73±1.89%ID/g，而A549肿瘤中为4.47±0.55%ID/g（P = 0.0219），阻断对照中为4.60±0.46%ID/g（P = 0.0228）。HT1376肿瘤达到10.63±1.35%ID/g，显著高于T24（4.10±0.89%ID/g，P = 0.0037）、阻断组（4.10±0.92%ID/g，P = 0.0036）和[Zr]Zr-DFO-IgG对照（5.67±0.90%ID/g，P = 0.0089）。H1975和HT1376肿瘤在48小时时的肿瘤与肌肉比值分别为14.30±2.02和15.00±1.62，表明对比度良好。用IRDye 800CW-度伐利尤单抗进行的荧光成像进一步证实了在PD-L1特异性肿瘤中的摄取。主要器官未观察到明显的组织学异常。估计人体有效剂量为0.0522 mSv/MBq。
[Zr]Zr-DFO-度伐利尤单抗能够对表达PD-L1的NSCLC和膀胱癌进行特异性、高对比度的免疫正电子发射断层扫描和荧光成像。这种双模态成像平台在无创评估PD-L1状态和个性化免疫治疗规划方面具有潜力。
