Synthesis and Biological Evaluation of Novel 99mTc-Tricarbonyl-Labeled Small-Molecule SPECT Tracers for PD-L1 Imaging

Utilizing radiotracers combined with nuclear imaging techniques to evaluate programmed death protein ligand 1 (PD-L1) expression is valuable for guiding programmed death protein 1 (PD-1)/PD-L1 checkpoint inhibitor therapy. However, the development of small-molecule radiotracers labeled with metallic radionuclides is challenging because of the complicated interactions between the small-molecule radiotracers and PD-L1 dimers. To address this challenge, novel 99mTc-labeled radiotracers were designed and synthesized through an “integrated strategy” in this study. The scaffold and polar tail chain lengths were modified to investigate their influence on the interaction between the radiotracer and PD-L1. The results demonstrated that the scaffold had little influence on PD-L1 affinity but had a significant effect on the pharmacokinetic properties of the radiotracer in vivo. The biodistribution and subsequent molecular docking results suggested that both the core structure and the polar tail chain length of the [99mTc]Tc-labeled radiotracers could contribute to the interaction with the PD-L1 dimer.