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Magnetic Resonance Imaging of Fibroblast Activation Protein Using a Targeted Gadolinium-Based Contrast Agent.

Dinghu Weng1,2,3, Rong Guo4,5, Changling Dong6

  • 1Department of Medical Imaging, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan 430071, Hubei, China.

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This study synthesized Gd-DOTA-FAPI04, a novel MRI contrast agent targeting fibroblast activation protein (FAP). In vivo studies demonstrated its effective accumulation in FAP-positive tumors, showing promise for cancer imaging.

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Gd-DOTA-FAPI04MRcontrast agentfibroblast activation proteinfibrotic lesions

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Area of Science:

  • Biomedical Imaging
  • Radiochemistry
  • Oncology

Background:

  • Fibroblast activation protein (FAP) is highly expressed in various tumors.
  • Targeted imaging agents can improve diagnostic accuracy for FAP-positive cancers.
  • Gadolinium-based contrast agents are essential for Magnetic Resonance Imaging (MRI).

Purpose of the Study:

  • To synthesize a novel quinoline-based MRI contrast agent, Gd-DOTA-FAPI04.
  • To evaluate the targeting capacity and efficacy of Gd-DOTA-FAPI04 for FAP-positive tumors in vivo.
  • To assess the safety profile of the novel contrast agent.

Main Methods:

  • Gd-DOTA-FAPI04 was synthesized by conjugating a gadolinium(III)-DOTA complex with FAP inhibitor FAPI04.
  • Longitudinal relaxation time (T1) and relaxivity were measured.
  • Cytotoxicity was assessed using the CCK-8 assay.
  • In vivo MRI was performed on mice bearing FAP-expressing tumors, with and without FAPI04 pre-blockade.
  • Immunohistochemistry was used to confirm FAP expression in tumor tissues.

Main Results:

  • Gd-DOTA-FAPI04 exhibited a higher longitudinal relaxivity (5.323 mM⁻¹s⁻¹) compared to gadodiamide (3.734 mM⁻¹s⁻¹).
  • The CCK-8 assay indicated minimal cytotoxicity of Gd-DOTA-FAPI04.
  • In vivo MRI revealed peak accumulation of Gd-DOTA-FAPI04 in FAP-positive tumors 1 hour post-injection.
  • Pre-injection with excess FAPI04 blocked tumor accumulation, confirming FAP-specific targeting.
  • Immunohistochemistry validated FAP expression in the tumor models.

Conclusions:

  • Gd-DOTA-FAPI04 is a safe and effective MRI contrast agent for targeting FAP-positive tumors.
  • The agent demonstrates specific tumor accumulation and holds potential for in vivo imaging of FAP.
  • This novel agent could advance the diagnostic capabilities in oncology for FAP-expressing malignancies.