Preclinical evaluation of [⁶⁸Ga]Ga-MRCP: a potential radiotracer for imaging PD-L1 expression in colorectal cancer

Area of Science:

• Nuclear medicine
• Oncology
• Radiochemistry

Background:

• Immune checkpoint inhibitors have advanced colorectal cancer treatment.
• Identifying immunotherapy responders and evaluating treatment efficacy are critical clinical challenges.

Purpose of the Study:

• To develop a novel positron emission tomography (PET) tracer for noninvasive detection of tumor programmed death-ligand 1 (PD-L1) expression.
• To assess the tracer's utility in evaluating immunotherapy efficacy in colorectal cancer.

Main Methods:

• A cyclic peptide-based PET tracer, [68Ga]Ga-MRCP, was synthesized using a mild radiolabeling method.
• In vitro binding affinity, cellular uptake, and in vivo PET imaging studies were performed.
• The tracer's ability to monitor dynamic changes in PD-L1 expression during immunotherapy was evaluated.

Main Results:

• [68Ga]Ga-MRCP was produced with high radiochemical yield, purity, and stability.
• The tracer demonstrated moderate binding affinity for PD-L1 (KD = 43.58 ± 6.48 nM).
• Significantly higher tracer uptake was observed in PD-L1 high-expression cells and tumors compared to low-expression counterparts.
• PET imaging confirmed specific tumor uptake and showed potential for dynamic PD-L1 monitoring during immunotherapy.

Conclusions:

• [68Ga]Ga-MRCP is a promising PET tracer for specifically targeting and visualizing PD-L1 expression in vivo.
• This tracer holds potential for noninvasively assessing immunotherapy eligibility and monitoring treatment response in colorectal cancer.