Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Folate receptor α (FRα) is overexpressed in many ovarian cancers, correlating with drug resistance and poor prognosis.
• Targeted therapies and imaging agents for FRα-positive cancers are crucial for improving patient outcomes.

Purpose of the Study:

• To develop and characterize a novel radiotracer, [⁶⁴Cu]Cu-O5, for targeting FRα in ovarian cancer.
• To evaluate the in vitro and in vivo performance of [⁶⁴Cu]Cu-O5 for imaging FRα-positive tumors.

Main Methods:

• Synthesis and radiolabeling of compound O5 with Copper-64 ([⁶⁴Cu]).
• In vitro cell uptake studies in FRα-positive IGROV1 cells and subcellular fractionation.
• In vivo positron emission tomography (PET) imaging in mice bearing IGROV1 xenografts.

Main Results:

• [⁶⁴Cu]Cu-O5 was synthesized with high molar activity and demonstrated stability in human serum.
• High specific uptake of [⁶⁴Cu]Cu-O5 was observed in FRα-positive cells, with significant association with cytoplasmic and nuclear fractions.
• PET imaging revealed clear tumor uptake of [⁶⁴Cu]Cu-O5 in xenograft models, with minimal liver accumulation and high tumor-to-background ratios.

Conclusions:

• [⁶⁴Cu]Cu-O5 is a promising FRα-targeting radiotracer with favorable preclinical characteristics for ovarian cancer imaging.
• The observed high cellular uptake and tumor targeting suggest potential for clinical translation in diagnosing and monitoring FRα-expressing cancers.