Preclinical PET Imaging of Tumor Cell Death following Therapy Using Gallium-68-Labeled C2Am

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Early detection of tumor cell death is crucial for evaluating cancer treatment efficacy.
• Current imaging methods have limitations in visualizing treatment-induced cell death.
• There is a need for novel imaging agents to monitor treatment response.

Purpose of the Study:

• To develop and evaluate 68Ga-labeled C2Am as a positron emission tomography (PET) tracer for imaging tumor cell death.
• To assess the synthesis, binding affinity, and in vivo performance of 68Ga-C2Am.
• To determine the potential clinical utility of 68Ga-C2Am for early treatment response assessment.

Main Methods:

• A one-pot synthesis of 68Ga-C2Am was optimized for rapid radiolabeling with high purity (>95%).
• In vitro binding assays were performed using human breast and colorectal cancer cell lines.
• In vivo studies involved dynamic PET imaging in mice bearing colorectal tumors treated with a TRAIL-R2 agonist.

Main Results:

• 68Ga-C2Am was synthesized efficiently within 20 minutes at room temperature.
• The tracer demonstrated binding to both apoptotic and necrotic tumor cells in vitro.
• In vivo PET imaging showed favorable biodistribution with predominantly renal clearance and low off-target organ uptake.
• A significant tumor-to-muscle ratio (2.3 ± 0.4) was achieved at 2h post-injection and 24h post-treatment.

Conclusions:

• 68Ga-C2Am is a promising phosphatidylserine-binding agent for PET imaging of tumor cell death.
• The rapid synthesis and favorable pharmacokinetic profile support its potential clinical translation.
• This tracer could enable early assessment of therapeutic response in cancer treatment.