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Related Experiment Video

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An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use
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Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various

Lifang Liu1,2, Jiawei Zhong3, Ziqi Zhang3

  • 1Nuclear Medicine Department, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, China.

European Journal of Nuclear Medicine and Molecular Imaging
|February 7, 2024
PubMed
Summary
This summary is machine-generated.

A novel tracer, [18F]FAP-2286, demonstrates high specificity and uptake for fibroblast-activated protein (FAP) in preclinical and clinical cancer imaging. This FAP-targeting agent shows promise as an alternative to 2-[18F]FDG PET for certain non-avid cancers.

Keywords:
Al18F-PET/CTClinical conversionFAP-2286Fibroblast activation protein-α

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Area of Science:

  • Radiochemistry and Nuclear Medicine
  • Oncology
  • Molecular Imaging

Background:

  • Fibroblast-activated protein (FAP) is a transmembrane protease highly expressed on cancer-associated fibroblasts (CAFs) in many solid tumors.
  • FAP expression is significantly lower or absent in normal tissues, making it an attractive target for cancer imaging and therapy.
  • Current imaging agents have limitations, necessitating the development of novel, high-performance tracers.

Purpose of the Study:

  • To develop and characterize a novel FAP-specific positron emission tomography (PET) tracer, [18F]FAP-2286.
  • To evaluate the preclinical performance of [18F]FAP-2286 in comparison to existing agents like [18F]FAPI-42 and [68Ga]Ga-FAP-2286.
  • To assess the clinical utility of [18F]FAP-2286 in patients with various cancers, comparing it with 2-[18F]FDG PET.

Main Methods:

  • [18F]FAP-2286 was synthesized under Good Manufacturing Practice (GMP) conditions.
  • In vitro assays included cell uptake, competitive binding affinity, internalization, and efflux studies using HT-1080hFAP cells.
  • In vivo studies involved PET imaging and biodistribution in tumor-bearing mice models and a pilot clinical study in 15 cancer patients.

Main Results:

  • [18F]FAP-2286 achieved a radiolabeling yield of 30.53 ± 5.20% with >97% radiochemical purity.
  • In vitro, the tracer exhibited specific uptake, high internalization, and low efflux.
  • PET imaging revealed rapid tumor uptake and satisfactory retention in both preclinical models and cancer patients.

Conclusions:

  • [18F]FAP-2286 demonstrates superior imaging characteristics, including rapid and high target uptake and sustained retention.
  • The tracer shows potential as an effective tool for early or delayed phase PET imaging.
  • [18F]FAP-2286 may serve as a valuable alternative for imaging cancers that are non-avid to 2-[18F]FDG, particularly those with low glucose metabolism.