Molecular imaging of angiogenesis after myocardial infarction by (111)In-DTPA-cNGR and (99m)Tc-sestamibi dual-isotope myocardial SPECT

G. Hendrikx, M. De Saint-Hubert, I. Dijkgraaf, M. Bauwens, K. Douma, R. Wierts, I. Pooters, N.M. van den Akker, T.M. Hackeng, M.J. Post, F.M. Mottaghy

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: CD13 is selectively upregulated in angiogenic active endothelium and can serve as a target for molecular imaging tracers to non-invasively visualise angiogenesis in vivo. Non-invasive determination of CD13 expression can potentially be used to monitor treatment response to pro-angiogenic drugs in ischemic heart disease. CD13 binds peptides and proteins through binding to tripeptide asparagine-glycine-arginine (NGR) amino acid residues. Previous studies using in vivo fluorescence microscopy and magnetic resonance imaging indicated that cNGR tripeptide-based tracers specifically bind to CD13 in angiogenic vasculature at the border zone of the infarcted myocardium. In this study, the CD13-binding characteristics of an (111)In-labelled cyclic NGR peptide (cNGR) were determined. To increase sensitivity, we visualised (111)In-DTPA-cNGR in combination with (99m)Tc-sestamibi using dual-isotope SPECT to localise CD13 expression in perfusion-deficient regions. METHODS: Myocardial infarction (MI) was induced in Swiss mice by ligation of the left anterior descending coronary artery (LAD). (111)In-DTPA-cNGR and (99m)Tc-sestamibi dual-isotope SPECT imaging was performed 7 days post-ligation in MI mice and in control mice. In addition, ex vivo SPECT imaging on excised hearts was performed, and biodistribution of (111)In-DTPA-cNGR was determined using gamma counting. Binding specificity of (111)In-DTPA-cNGR to angiogenic active endothelium was determined using the Matrigel model. RESULTS: Labelling yield of (111)In-DTPA-cNGR was 95% to 98% and did not require further purification. In vivo, (111)In-DTPA-cNGR imaging showed a rapid clearance from non-infarcted tissue and a urinary excretion of 82% of the injected dose (I.D.) 2 h after intravenous injection in the MI mice. Specific binding of (111)In-DTPA-cNGR was confirmed in the Matrigel model and, moreover, binding was demonstrated in the infarcted myocardium and infarct border zone. CONCLUSIONS: Our newly designed and developed angiogenesis imaging probe (111)In-DTPA-cNGR allows simultaneous imaging of CD13 expression and perfusion in the infarcted myocardium and the infarct border zone by dual-isotope micro-SPECT imaging.
Original languageEnglish
Article number2
Pages (from-to)13-22
Number of pages10
JournalEJNMMI Research
Volume5
DOIs
Publication statusPublished - 28 Jan 2015

Keywords

  • Myocardial infarction
  • Angiogenesis
  • CD13
  • Micro-SPECT
  • FIBROBLAST-GROWTH-FACTOR
  • TRANSMYOCARDIAL LASER REVASCULARIZATION
  • CORONARY-ARTERY-DISEASE
  • THERAPEUTIC ANGIOGENESIS
  • REFRACTORY ANGINA
  • GENE-TRANSFER
  • HOMING MOTIF
  • BLOOD-FLOW
  • PEPTIDES
  • ISCHEMIA

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