[⁶⁸Ga]Ga-NODAGA-RGD post MI reflects activated fibroblasts rather than angiogenesis

Area of Science:

• Cardiovascular Research
• Molecular Imaging
• Integrin Biology

Background:

• Angiogenesis is vital for myocardial healing post-myocardial infarction (MI).
• Alpha-v-beta-3 (α_vβ₃)-integrin is a key regulator of angiogenesis.
• RGD-based PET tracers, like [⁶⁸Ga]Ga-NODAGA-RGD, target α_vβ₃-integrin for imaging, but specificity is limited.

Purpose of the Study:

• To identify the specific cell type expressing the highest α_vβ₃-integrin during myocardial healing.
• To determine the actual value of [⁶⁸Ga]Ga-NODAGA-RGD for imaging post-MI angiogenesis by assessing its target specificity.

Main Methods:

• Two myocardial infarction (MI) models were created: permanent ligation (PL) and transient ischemia/reperfusion (I/R).
• Cardiac magnetic resonance imaging (CMR) assessed cardiac function and morphology.
• Histology, immunohistology, PET imaging with [⁶⁸Ga]Ga-NODAGA-RGD, and single-nucleus transcriptomics were performed.

Main Results:

• PET imaging showed higher tracer accumulation in the PL group's infarct area compared to the I/R group.
• Single-nucleus transcriptomics revealed enriched angiogenesis markers in the I/R group.
• The highest α_vβ₃-integrin mRNA expression was found in activated fibroblast clusters, not angiogenic cells.

Conclusions:

• Activated fibroblasts are the primary cellular targets of [⁶⁸Ga]Ga-NODAGA-RGD post-MI.
• The tracer is likely not suitable for imaging angiogenesis in the early stages after myocardial infarction.
• Further research is needed to identify specific tracers for imaging post-MI angiogenesis.