Programmed
death ligand 1 (PDL1) is a
specific molecular target for the diagnosis and immunotherapy of solid
tumors. PET imaging can be used for noninvasive assessments of PDL1
expression in tumors to aid in therapy selection. The most frequently
reported small-molecule radiotracer of PDL1 is limited by low imaging
specificity, short residence time, and singular functionality. Here,
we combined a biocompatible melanin nanoprobe with the PDL1-binding
peptide WL12 to construct a novel radiotracer, 124I-WPMN,
to enhance PDL1 targeting. The radiochemical purity of 124I-WPMN was >95%, and uptake in A549PDL1 cells was 1.49
± 0.08% at 2 h. The uptake was blocked by WL12 (0.39 ± 0.03%, P < 0.0001). This novel radiotracer showed a higher affinity
for PDL1 (K
d = 18.5 nM) than 68Ga-NOTA-WL12 (K
d = 24.0 nM). Micro-PET/CT
imaging demonstrated specific uptake and a high signal-to-noise ratio
in an A549PDL1 xenograft mouse model with a tumor-to-muscle
ratio of 27.31 ± 7.03 at 2 h. The levels increased or remained
steady for more than 72 h, and tumor uptake was significantly higher
than 68Ga-NOTA-WL12, at 6.08 ± 0.62 at 2 h. Prolonged
retention of 124I-WPMN makes it possible to conduct PET/MRI
imaging over long periods and to perform various imaging techniques.
A clear advantage of 124I-WPMN over 68Ga-NOTA-WL12
was observed for PDL1-targeted PET imaging after nanoparticle modification,
supporting the utility of 124I-WPMN PET imaging as an effective
diagnostic tool for optimizing PDL1-targeted therapies.