Fibroblast Activation Protein-Targeted SPECT Imaging Using ^99mTc: A Comprehensive Review

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Fibroblast Activation Protein (FAP) is highly expressed in cancer-associated fibroblasts within the tumor microenvironment of most epithelial malignancies.
• FAP's tumor-selective expression makes it an attractive target for molecular imaging and theranostics.
• Positron Emission Tomography (PET) FAP inhibitors (FAPI) show clinical promise but face limitations in cost and accessibility.

Purpose of the Study:

• To review recent advancements in Technetium-99m (99mTc)-labeled FAPI radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) imaging.
• To summarize 99mTc radiolabeling strategies and evaluate their preclinical and clinical performance.
• To highlight the potential of 99mTc-FAPI as a globally accessible alternative for FAP-targeted imaging.

Main Methods:

• Systematic review of literature on 99mTc-labeled FAPI development.
• Description of various 99mTc coordination strategies for radiolabeling (e.g., oxo, nitrido, tricarbonyl, isonitrile, HYNIC).
• Analysis of preclinical and clinical data regarding tumor uptake, pharmacokinetics, and imaging quality.

Main Results:

• Multiple 99mTc-labeling strategies have been successfully developed for FAPI targeting.
• 99mTc-FAPI radiotracers demonstrate high tumor uptake and favorable pharmacokinetic profiles.
• SPECT imaging with 99mTc-FAPI provides excellent imaging contrast for visualizing FAP expression.

Conclusions:

• 99mTc-labeled FAPI radiopharmaceuticals represent a cost-effective and widely accessible imaging modality for FAP.
• These tracers exhibit promising characteristics for clinical translation in FAP-targeted molecular imaging.
• SPECT imaging with 99mTc-FAPI offers a viable alternative to PET-based approaches, especially where PET infrastructure is limited.