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

Hendrikx G, De Saint-Hubert M, Dijkgraaf I, Bauwens M, Douma K, Wierts R, Pooters I, Van den Akker NM, Hackeng TM, Post MJ, Mottaghy FM - EJNMMI Res (2015)

Bottom Line: Labelling yield of (111)In-DTPA-cNGR was 95% to 98% and did not require further purification.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Maastricht University Medical Centre (MUMC+), Postbox 5800, 6202 AZ Maastricht, The Netherlands ; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

Overview of cardiac 17 segment models for99mTc-sestamibi and111In-DTPA-cNGR SUVs. In healthy control hearts and MI hearts. (a) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 99mTc-sestamibi SUVs per segment. (b) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 111In-DTPA-cNGR SUVs per segment. Statistical significance was indicated as asterisk (*) (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4384708&req=5

Fig3: Overview of cardiac 17 segment models for99mTc-sestamibi and111In-DTPA-cNGR SUVs. In healthy control hearts and MI hearts. (a) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 99mTc-sestamibi SUVs per segment. (b) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 111In-DTPA-cNGR SUVs per segment. Statistical significance was indicated as asterisk (*) (p < 0.05).

Mentions: Standardised uptake values (SUVs) of 99mTc-sestamibi were significantly decreased in the anterolateral region of the left ventricle in infarcted hearts compared to those in the healthy control mice (Table 2 and Figure 3a). In the MI mice, six segments displayed significantly higher 111In-DTPA-cNGR uptake compared to that in the healthy control hearts (Table 1 and Figure 3b), of which three had significantly lower 99mTc-sestamibi uptake. The six segments that displayed significantly enhanced 111In-DTPA-cNGR uptake were all located in the infarcted myocardium or in the infarct border zone.Table 2


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

Hendrikx G, De Saint-Hubert M, Dijkgraaf I, Bauwens M, Douma K, Wierts R, Pooters I, Van den Akker NM, Hackeng TM, Post MJ, Mottaghy FM - EJNMMI Res (2015)

Overview of cardiac 17 segment models for99mTc-sestamibi and111In-DTPA-cNGR SUVs. In healthy control hearts and MI hearts. (a) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 99mTc-sestamibi SUVs per segment. (b) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 111In-DTPA-cNGR SUVs per segment. Statistical significance was indicated as asterisk (*) (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384708&req=5

Fig3: Overview of cardiac 17 segment models for99mTc-sestamibi and111In-DTPA-cNGR SUVs. In healthy control hearts and MI hearts. (a) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 99mTc-sestamibi SUVs per segment. (b) Cardiac 17 segment models of the healthy control mice and the MI mice indicating colour-coded average 111In-DTPA-cNGR SUVs per segment. Statistical significance was indicated as asterisk (*) (p < 0.05).
Mentions: Standardised uptake values (SUVs) of 99mTc-sestamibi were significantly decreased in the anterolateral region of the left ventricle in infarcted hearts compared to those in the healthy control mice (Table 2 and Figure 3a). In the MI mice, six segments displayed significantly higher 111In-DTPA-cNGR uptake compared to that in the healthy control hearts (Table 1 and Figure 3b), of which three had significantly lower 99mTc-sestamibi uptake. The six segments that displayed significantly enhanced 111In-DTPA-cNGR uptake were all located in the infarcted myocardium or in the infarct border zone.Table 2

Bottom Line: Labelling yield of (111)In-DTPA-cNGR was 95% to 98% and did not require further purification.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Maastricht University Medical Centre (MUMC+), Postbox 5800, 6202 AZ Maastricht, The Netherlands ; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus