Formulation and Preclinical Testing of Tc-99m-Labeled HYNIC-Glc-FAPT as a FAP-Targeting Tumor Radiotracer

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Fibroblast activation protein (FAP) is a target for cancer imaging and therapy.
• Current positron emission tomography (PET) probes are costly.
• Development of single-photon imaging agents is needed.

Purpose of the Study:

• To synthesize and evaluate novel technetium-99m (99mTc) labeled fibroblast activation protein inhibitor (FAPI) targeting peptide probes.
• To investigate the potential of these agents for single-photon emission computed tomography (SPECT) imaging of FAP-expressing cancers.

Main Methods:

• Synthesis of HYNIC-Glc-FAPT.
• Radiolabeling with 99mTc using tricine/EDDA or dimer tricine as coligands.
• In vitro characterization including stability, cellular uptake, and affinity assays.
• In vivo SPECT imaging and biodistribution studies in tumor-bearing mice.

Main Results:

• Two 99mTc-labeled FAPI probes, [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT and [99mTc]Tc-tricine(2)-HYNIC-Glc-FAPT, were synthesized with high radiochemical yields (>97%).
• [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT demonstrated favorable hydrophilic properties, high FAP-specificity, and affinity.
• In vivo studies showed sustained tumor uptake and rapid clearance from non-target organs for [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT.

Conclusions:

• Successful synthesis of two novel 99mTc-labeled FAPI probes.
• [99mTc]Tc-tricine/EDDA-HYNIC-FAPT exhibits excellent targeting properties for FAP-expressing tumors.
• This agent holds potential for cost-effective SPECT imaging and prognostic evaluation in advanced-stage malignancies.