Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors

Area of Science:

• Nuclear medicine
• Radiochemistry
• Molecular imaging
• Cancer immunotherapy

Background:

• Programmed cell death receptor 1 (PD-1) and its ligand PD-L1 are crucial immune checkpoints in cancer.
• Positron emission tomography (PET) imaging offers dynamic monitoring of PD-L1 expression for treatment response prediction.
• Development of targeted radiotracers is essential for effective PD-L1 visualization.

Purpose of the Study:

• To synthesize and validate two novel linear peptide-based radiotracers, [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202, for PD-L1 imaging.
• To evaluate the diagnostic potential of these tracers in preclinical cancer models.
• To compare the performance of the new tracers with existing ones.

Main Methods:

• Synthesis and radiolabeling of peptide precursors HKP2201 (derived from CLP002) and HKP2202 (dimerized HKP2201) with Copper-64 (64Cu) and Gallium-68 (68Ga).
• In vitro studies including cellular uptake, binding assays, and competitive blocking on PD-L1 expressing cell lines (B16F10, MC38).
• In vivo studies using PET imaging and ex vivo biodistribution in tumor-bearing mouse models.

Main Results:

• Satisfactory radiocharacteristics were achieved for both [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202.
• Tracers demonstrated specific binding to PD-L1 with concentration-dependent affinity and comparable EC50 values to WL12.
• [64Cu]/[68Ga]HKP2202 showed higher tumor uptake than [64Cu]/[68Ga]HKP2201; 64Cu-tracers exhibited longer tumor retention than 68Ga-tracers, with lower liver accumulation for 68Ga-tracers.

Conclusions:

• The novel radiotracers [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 are promising for visualizing PD-L1 status in preclinical settings.
• These tracers offer potential for rapid detection of primary and metastatic tumors, including hepatic carcinoma.
• Further clinical evaluation is warranted to determine their full clinical utility in cancer diagnosis and treatment guidance.