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<p>Programmed death-ligand 1 (PD-L1) represents a pivotal target for immune checkpoint blockade therapy. This study developed a novel PD-L1-targeting SPECT probe [<sup>99m</sup>Tc]Tc-G<sub>3</sub>C-2CBM based on dimeric 2-bromo-3-biphenyl (CBM) scaffold design. The probe was designed to enable bivalent interactions through dual CBM domains, exhibiting &gt; 98% radiochemical yield and excellent in vitro stability. Cellular uptake studies revealed significantly higher accumulation in PD-L1-overexpressing A375-hPD-L1 cells compared to A375 cells (14.15 ± 2.11% vs. 5.89 ± 0.55% at 4&#xa0;h; uptake ratio = 3.20). The probe displayed favorable binding affinity (K<sub>D</sub> = 36.54 ± 7.28&#xa0;nM) and inhibitory potency (IC<sub>50</sub> = 69.62 ± 5.15&#xa0;nM). In vivo SPECT imaging confirmed tumor-specific accumulation, though accompanied by notable hepatic uptake. These results demonstrate that CBM dimerization is a feasible approach for retaining PD-L1 binding and may provide a basis for the future development of multivalent radiotracers.</p>

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Synthesis and preliminary evaluation of a 99mTc-labeled bivalent radiotracer targeting PD-L1

  • 期刊论文

  • 发表日期：

    2026年1月23日

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  • Yiyin Mao,
  • Peng Zhou,
  • Juntao Jiang,
  • Yaling Liu,
  • Hongyong Wang,
  • Guoqing Han,
  • Jun Wu,
  • Pei Zou,
  • Chunxiong Lu

摘要

Programmed death-ligand 1 (PD-L1) represents a pivotal target for immune checkpoint blockade therapy. This study developed a novel PD-L1-targeting SPECT probe [99mTc]Tc-G3C-2CBM based on dimeric 2-bromo-3-biphenyl (CBM) scaffold design. The probe was designed to enable bivalent interactions through dual CBM domains, exhibiting > 98% radiochemical yield and excellent in vitro stability. Cellular uptake studies revealed significantly higher accumulation in PD-L1-overexpressing A375-hPD-L1 cells compared to A375 cells (14.15 ± 2.11% vs. 5.89 ± 0.55% at 4 h; uptake ratio = 3.20). The probe displayed favorable binding affinity (KD = 36.54 ± 7.28 nM) and inhibitory potency (IC50 = 69.62 ± 5.15 nM). In vivo SPECT imaging confirmed tumor-specific accumulation, though accompanied by notable hepatic uptake. These results demonstrate that CBM dimerization is a feasible approach for retaining PD-L1 binding and may provide a basis for the future development of multivalent radiotracers.