Molecular Imaging of Fibroblast Activity After Myocardial Infarction Using a 68Ga-Labeled Fibroblast Activation

Zohreh Varasteh1, Sarajo Mohanta2,3, Stephanie Robu4

  • 1Department of Nuclear Medicine, Klinikum rechts der Isar der TUM, Munich, Germany zohreh.varasteh@tum.de.

Insights

New PET imaging using 68Ga-FAPI-04 effectively visualizes activated fibroblasts after myocardial infarction (MI). This tracer shows potential for monitoring cardiac remodeling and improving patient management following heart attacks.

Area of Science:

  • Nuclear Medicine
  • Cardiovascular Imaging
  • Radiochemistry

Background:

  • Heart failure is a significant complication following myocardial infarction (MI).
  • Activated fibroblasts in the injured heart influence cardiac remodeling post-MI.
  • Fibroblast Activation Protein (FAP) is a marker of activated fibroblasts.

Purpose of the Study:

  • To assess the feasibility of using a novel 68Ga-labeled FAP inhibitor (68Ga-FAPI-04) for PET imaging of fibroblast activation.
  • To evaluate 68Ga-FAPI-04 as a tool for monitoring cardiac remodeling after MI in a preclinical model.

Main Methods:

  • Myocardial infarction (MI) and sham-operated rats underwent 68Ga-FAPI-04 PET/CT scans at multiple time points post-MI.
  • Comparative 18F-FDG PET/CT scans were performed 3 days after MI.
  • Ex vivo analyses included autoradiography, H&E staining, and immunofluorescence on harvested heart tissues.

Main Results:

  • 68Ga-FAPI-04 uptake in the injured myocardium peaked at 6 days post-MI.
  • Tracer accumulation was concentrated in the MI border zone, correlating with FAP-positive myofibroblast presence.
  • Blocking studies demonstrated specific uptake, with minimal off-target accumulation.

Conclusions:

  • 68Ga-FAPI-04 is a promising radiotracer for noninvasive in vivo imaging of post-MI fibroblast activation.
  • This imaging approach may offer significant diagnostic and prognostic value for managing patients after MI.
  • Monitoring activated fibroblasts could enhance understanding and treatment of cardiac remodeling.

Related Concept Videos

Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.8K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
11.2K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.4K
Activation Energy01:26

Activation Energy

Activation energy is the minimum amount of energy necessary for a chemical reaction to move forward. The higher the activation energy, the slower the rate of the reaction. However, adding heat to the reaction will increase the rate, since it causes molecules to move faster and increase the likelihood that molecules will collide. The collision and breaking of bonds represents the uphill phase of a reaction and generates the transition state. The transition state is an unstable high-energy state...
86.4K
tRNA Activation02:26

tRNA Activation

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
22.6K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.6K