^99mTc-Labeled Quinolone-Based Novel Skeletal Tracers for Tumor Visualization through Fibroblast Activation Protein

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Oncology

Background:

• Fibroblast activation protein (FAP) is a key target for cancer diagnosis.
• Positron Emission Tomography (PET) tracers for FAP are clinically feasible.
• Technetium-99m (99mTc)-labeled FAP Single Photon Emission Computed Tomography (SPECT) tracers are underrepresented in clinical studies.

Purpose of the Study:

• To develop novel 99mTc-labeled FAP SPECT tracers with improved pharmacokinetic properties.
• To address the limitations of existing quinoline-derived 99mTc-FAPI tracers, such as low tumor uptake.
• To enhance the clinical applicability of FAP-targeted SPECT imaging.

Main Methods:

• Utilized scaffold hopping and conformational constrained strategies to design a novel quinolone-based pharmacophore.
• Conducted serial screening and preclinical evaluations of new tracer candidates.
• Assessed the performance of the lead candidate, 99mTc-FAPI-YQ3, in preclinical models and four oncology patients.

Main Results:

• The novel 99mTc-FAPI-YQ3 tracer demonstrated exceptionally high tumor uptake.
• 99mTc-FAPI-YQ3 exhibited superior pharmacokinetic properties compared to existing tracers.
• The tracer showed reliable safety and clinical efficacy in oncology patients.

Conclusions:

• 99mTc-FAPI-YQ3 is a promising radiotracer for FAP-targeted cancer diagnosis.
• This novel tracer significantly advances SPECT molecular imaging for oncology.
• The developed tracer holds potential for improved clinical application in cancer detection.