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Evaluation of Chelator-to-Antibody Ratio on Development of 89 Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

Shih-Chuan TsaiShiou-Shiow FarnWei-Lin LoFang-Yu Ou YangYong-Ching KangLiang-Cheng ChenKuo-Ting ChenJiunn Wang LiaoJui-Yin KungJenn-Tzong ChenFeng-Yun J Huang
Published in: International journal of molecular sciences (2023)
89 Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89 Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89 Zr-DFO-anti-PD-L1-mAb_3X ( tracer_3X ), 89 Zr-DFO-anti-PD-L1-mAb_10X ( tracer_10X ), and 89 Zr-DFO-anti-PD-L1-mAb_20X ( tracer_20X ). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89 Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X , tracer_10X , and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89 Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X , tracer_10X , and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X , tracer_10X , and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89 Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89 Zr-iPET tracers.
Keyphrases
  • pet imaging
  • positron emission tomography
  • computed tomography
  • high resolution
  • mouse model
  • monoclonal antibody
  • bone marrow
  • case report
  • big data
  • single cell
  • cell therapy
  • pet ct
  • data analysis