Initial evaluation of Cu-64 labeled PARPi-DOTA PET imaging in mice with mesothelioma

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Poly(ADP-ribose) polymerase (PARP) is a key molecular target in oncology.
• PARP is overexpressed in mesothelioma, making it a potential target for diagnosis and therapy.
• Olaparib-based molecular probes have been developed for tumor imaging.

Purpose of the Study:

• To synthesize and evaluate a novel Olaparib analogue containing a DOTA moiety for Copper-64 radiolabeling.
• To assess the utility of this Copper-64 labeled compound as a positron emission tomography (PET) tracer for mesothelioma.
• To investigate the in vivo tumor targeting and diagnostic potential in mesothelioma models.

Main Methods:

• Synthesis of an Olaparib analogue with a DOTA chelator.
• Radiolabeling with Copper-64 (Cu-64) achieving high yield and purity.
• In vivo biodistribution studies and PET imaging at multiple time points.
• Comparison of tumor uptake between the study group and control group.

Main Results:

• Successful synthesis and radiolabeling of the Olaparib-DOTA analogue with Cu-64.
• High radiochemical purity (>99%) and labeling yield (90%) were achieved.
• Significant higher tumor uptake was observed in the mesothelioma model compared to controls (3.45±0.47% ID/g vs 2.26±0.30% ID/g).
• Mesothelioma tumors were clearly visualized by PET imaging.

Conclusions:

• The developed Cu-64 labeled Olaparib analogue is a feasible PET tracer for mesothelioma.
• This tracer demonstrates effective in vivo tumor targeting and detection.
• The findings support the development of Olaparib-based theranostic agents for mesothelioma.