Evaluation of Pan-SSTRs Targeted Radioligand [⁶⁴Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Oncology Imaging

Background:

• Somatostatin receptors (SSTRs) are crucial biomarkers for various neuroendocrine tumors.
• Developing targeted radiotracers for SSTRs is vital for accurate tumor diagnosis and management.
• Existing radiotracers may have limitations in targeting all SSTR subtypes.

Purpose of the Study:

• To synthesize and evaluate a new 64Cu-labeled pan-somatostatin receptor (pan-SSTR) probe, PA1.
• To assess the in vitro and in vivo performance of the [64Cu]NOTA-PA1 radiotracer.
• To determine its potential as a diagnostic imaging agent for SSTR-positive tumors.

Main Methods:

• Radiosynthesis of 64Cu-labeled NOTA-PA1 with high radiochemical purity and stability.
• In vitro cell uptake studies in various cancer cell lines (MCF-7, A549, BGC823, HT-29).
• In vivo biodistribution and micro-positron emission tomography (micro-PET) imaging in xenografted nude mice.

Main Results:

• [64Cu]NOTA-PA1 exhibited high specific activity, purity, and stability.
• Superior cell uptake of [64Cu]NOTA-PA1 compared to [64Cu]DOTA-TATE in tested cell lines.
• Effective tumor detection in vivo using micro-PET imaging in A549 and MCF-7 xenografts.

Conclusions:

• [64Cu]NOTA-PA1 shows promising high binding affinity and uptake for SSTRs.
• The tracer demonstrates excellent potential for in vivo imaging of SSTR-positive tumors.
• [64Cu]NOTA-PA1 could serve as a valuable multisubtype targeted radiotracer for SSTRs imaging.