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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

In vivoandex vivotransversal tomographic images of an infarcted mouse-heart. (a)In vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. Numerical values on the scale bars indicate the SUVmax and SUVmin. (b)Ex vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. (c) Polar perfusion maps combined with the 17 segment model show that enhanced 111In-DTPA-cNGR uptake (orange in areas 13, 16 and 17) occurred mainly in areas with low 99mTc-sestamibi uptake (green in areas 13, 16 and 17), signifying the anterolateral region in the infarcted myocardium.
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Fig2: In vivoandex vivotransversal tomographic images of an infarcted mouse-heart. (a)In vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. Numerical values on the scale bars indicate the SUVmax and SUVmin. (b)Ex vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. (c) Polar perfusion maps combined with the 17 segment model show that enhanced 111In-DTPA-cNGR uptake (orange in areas 13, 16 and 17) occurred mainly in areas with low 99mTc-sestamibi uptake (green in areas 13, 16 and 17), signifying the anterolateral region in the infarcted myocardium.

Mentions: Transversal tomographic images of the mouse hearts with MI showed decreased uptake of 99mTc-sestamibi in the anterolateral region of the left ventricle 7 days after LAD occlusion (Figure 2), indicating a perfusion defect. The uptake of 111In-DTPA-cNGR mirrored that of 99mTc-sestamibi in that the probe was taken up in areas of low perfusion. These uptake patterns were revealed on images of the in vivo scans and even more pronounced on images of the ex vivo scans (Figure 2). In non-infarcted hearts, the uptake of 99mTc-sestamibi was equally distributed over the whole myocardium while uptake of 111In-DTPA-cNGR was limited (data not shown).Figure 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)

In vivoandex vivotransversal tomographic images of an infarcted mouse-heart. (a)In vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. Numerical values on the scale bars indicate the SUVmax and SUVmin. (b)Ex vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. (c) Polar perfusion maps combined with the 17 segment model show that enhanced 111In-DTPA-cNGR uptake (orange in areas 13, 16 and 17) occurred mainly in areas with low 99mTc-sestamibi uptake (green in areas 13, 16 and 17), signifying the anterolateral region in the infarcted myocardium.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: In vivoandex vivotransversal tomographic images of an infarcted mouse-heart. (a)In vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. Numerical values on the scale bars indicate the SUVmax and SUVmin. (b)Ex vivo images of 111In-DTPA-cNGR uptake, mainly in areas of 99mTc-sestamibi absence. (c) Polar perfusion maps combined with the 17 segment model show that enhanced 111In-DTPA-cNGR uptake (orange in areas 13, 16 and 17) occurred mainly in areas with low 99mTc-sestamibi uptake (green in areas 13, 16 and 17), signifying the anterolateral region in the infarcted myocardium.
Mentions: Transversal tomographic images of the mouse hearts with MI showed decreased uptake of 99mTc-sestamibi in the anterolateral region of the left ventricle 7 days after LAD occlusion (Figure 2), indicating a perfusion defect. The uptake of 111In-DTPA-cNGR mirrored that of 99mTc-sestamibi in that the probe was taken up in areas of low perfusion. These uptake patterns were revealed on images of the in vivo scans and even more pronounced on images of the ex vivo scans (Figure 2). In non-infarcted hearts, the uptake of 99mTc-sestamibi was equally distributed over the whole myocardium while uptake of 111In-DTPA-cNGR was limited (data not shown).Figure 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