Imaging CDK4/6 Broaden Options of Breast Cancer Diagnostics with Positron Emission Tomography

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are crucial in treating certain breast cancers.
• Accurate patient selection is vital for effective CDK4/6 inhibitor therapy.
• Novel diagnostic tools are needed to predict treatment response.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) radiotracer for assessing CDK4/6 inhibitor sensitivity in breast cancer.
• To guide personalized treatment selection for breast cancer patients.

Main Methods:

• Synthesis and in vitro/in vivo evaluation of two CDK4/6-targeting precursors.
• Selection of three breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-468) based on palbociclib sensitivity.
• Comparison of [68Ga]Ga-DOTA-Hexa-CDKi and [68Ga]Ga-DOTA-Bua-CDKi using PET/CT imaging and blocking assays.
• Assessment of biosafety for diagnostic use.

Main Results:

• [68Ga]Ga-DOTA-Bua-CDKi demonstrated superior performance in identifying highly sensitive cell lines compared to [68Ga]Ga-DOTA-Hexa-CDKi.
• PET/CT imaging revealed significantly higher uptake of [68Ga]Ga-DOTA-Bua-CDKi in MCF-7 tumors (8.40 ± 0.85%ID/g at 60 min).
• Significant differences in tumor uptake were observed among the three models (P < 0.05), with specific tumor targeting confirmed by blocking assays.

Conclusions:

• [68Ga]Ga-DOTA-Bua-CDKi is a novel PET radiotracer with high specificity for CDK4/6.
• This tracer enables effective contrast imaging in tumor models and shows promise for evaluating patient response to CDK4/6 inhibitors.
• It represents a significant advancement in personalized medicine for breast cancer treatment.