^99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications

Alessandra Boschi ¹, Luca Urso ^2,3, Licia Uccelli ^4,5

⁰Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari, 46, 44121, Ferrara, Italy.

Ejnmmi Radiopharmacy and Chemistry +

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May 2, 2024

View abstract on PubMed

Summary

Technetium-99m labeled fibroblast activating protein inhibitors ([<sup>99m</sup>Tc]Tc-FAPi) offer a cost-effective alternative to PET imaging for detecting cancer and inflammatory diseases. Research explores various radiolabeling strategies to optimize tracer properties for improved diagnostic performance.

Area Of Science

Nuclear medicine and molecular imaging.
Radiochemistry and radiopharmaceutical development.
Oncology and inflammation research.

Background

Fibroblast activating protein (FAP) is a key biomarker overexpressed in cancer-associated fibroblasts and inflammatory conditions like liver cirrhosis and pulmonary fibrosis.
FAP-targeted positron emission tomography (PET) imaging has shown promise but is limited by high costs and technology availability.
Development of technetium-99m labeled FAP inhibitors ([<sup>99m</sup>Tc]Tc-FAPi) for single photon emission computed tomography (SPECT) aims to provide a more accessible imaging alternative.

Purpose Of The Study

To review radiochemical strategies for developing [<sup>99m</sup>Tc]Tc-FAPi tracers.
To highlight challenges and solutions in synthesizing and applying these tracers.
To summarize preclinical and clinical applications of [<sup>99m</sup>Tc]Tc-FAPi imaging in oncology and inflammatory diseases.

Main Methods

Investigated various radiolabeling approaches for FAP inhibitors with <sup>99m</sup>Tc, including mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies.
Evaluated tracer efficiency, binding affinity, specificity, and pharmacokinetic properties in vitro and in animal models.
Assessed diagnostic performance of [<sup>99m</sup>Tc]Tc-FAPi SPECT imaging in initial clinical studies.

Main Results

Multiple labeling strategies yielded efficient and high-affinity [<sup>99m</sup>Tc]Tc-FAPi tracers with demonstrated specificity for FAP-positive targets.
Challenges with lipophilicity led to hepatobiliary excretion; development of hydrophilic FAPi compounds improved biodistribution.
SPECT imaging with [<sup>99m</sup>Tc]Tc-FAPi showed promising results in patients with gastrointestinal tumors, gliomas, lung, breast, and cervical cancers, as well as in myocardial and idiopathic pulmonary fibrosis.

Conclusions

Various radiochemical strategies can produce effective [<sup>99m</sup>Tc]Tc-FAPi tracers, with ongoing efforts to optimize their properties.
Addressing challenges like lipophilicity is crucial for favorable pharmacokinetics and biodistribution.
[<sup>99m</sup>Tc]Tc-FAPi SPECT imaging represents a valuable and accessible tool for diagnosing and monitoring FAP-related cancers and inflammatory conditions.

Keywords:

Fibroblast activation protein Inflammation Molecular imaging Oncology PET SPECT