Multiparametric Evaluation of Post-MI Small Animal Models Using Metabolic ([18F]FDG) and Perfusion-Based (SYN1) Heart Viability Tracers

Int J Mol Sci. 2021 Nov 22;22(22):12591. doi: 10.3390/ijms222212591.

Abstract

Cardiovascular diseases (CVD), with myocardial infarction (MI) being one of the crucial components, wreak havoc in developed countries. Advanced imaging technologies are required to obtain quick and widely available diagnostic data. This paper describes a multimodal approach to in vivo perfusion imaging using the novel SYN1 tracer based on the fluorine-18 isotope. The NOD-SCID mice were injected intravenously with SYN1 or [18F] fluorodeoxyglucose ([18F]-FDG) radiotracers after induction of the MI. In all studies, the positron emission tomography-computed tomography (PET/CT) technique was used. To obtain hemodynamic data, mice were subjected to magnetic resonance imaging (MRI). Finally, the biodistribution of the SYN1 compound was performed using Wistar rat model. SYN1 showed normal accumulation in mouse and rat hearts, and MI hearts correctly indicated impaired cardiac segments when compared to [18F]-FDG uptake. In vivo PET/CT and MRI studies showed statistical convergence in terms of the size of the necrotic zone and cardiac function. This was further supported with RNAseq molecular analyses to correlate the candidate function genes' expression, with Serpinb1c, Tnc and Nupr1, with Trem2 and Aldolase B functional correlations showing statistical significance in both SYN1 and [18F]-FDG. Our manuscript presents a new fluorine-18-based perfusion radiotracer for PET/CT imaging that may have importance in clinical applications. Future research should focus on confirmation of the data elucidated here to prepare SYN1 for first-in-human trials.

Keywords: FDG; RNAseq of the heart tissue; SYN1; [18F]-FDG; fluorine radiotracers; molecular profiling after myocardial infarction; positron emission tomography–computed tomography (PET/CT).

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Contrast Media / pharmacology
  • Fluorodeoxyglucose F18 / pharmacology
  • Fructose-Bisphosphate Aldolase / genetics
  • Gene Expression Regulation / drug effects
  • Heart / diagnostic imaging*
  • Heart / drug effects
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Membrane Glycoproteins / genetics
  • Mice
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / pathology
  • Neoplasm Proteins / genetics*
  • Positron Emission Tomography Computed Tomography
  • Rats
  • Receptors, Immunologic / genetics
  • Serpins / genetics*
  • Tenascin / genetics*
  • Tissue Distribution / drug effects

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Contrast Media
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Nupr1 protein, rat
  • Receptors, Immunologic
  • Serpinb1a protein, mouse
  • Serpins
  • Tenascin
  • Tnc protein, mouse
  • Trem2 protein, mouse
  • trem2 protein, rat
  • Fluorodeoxyglucose F18
  • Fructose-Bisphosphate Aldolase