Dual-isotope Myocardial SPECT Research Articles

Molecular imaging of angiogenesis after myocardial infarction by 111In-DTPA-cNGR and 99mTc-sestamibi dual-isotope myocardial SPECT

BackgroundCD13 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 111In-labelled cyclic NGR peptide (cNGR) were determined. To increase sensitivity, we visualised 111In-DTPA-cNGR in combination with 99mTc-sestamibi using dual-isotope SPECT to localise CD13 expression in perfusion-deficient regions.MethodsMyocardial infarction (MI) was induced in Swiss mice by ligation of the left anterior descending coronary artery (LAD). 111In-DTPA-cNGR and 99mTc-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 111In-DTPA-cNGR was determined using gamma counting. Binding specificity of 111In-DTPA-cNGR to angiogenic active endothelium was determined using the Matrigel model.ResultsLabelling yield of 111In-DTPA-cNGR was 95% to 98% and did not require further purification. In vivo, 111In-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 111In-DTPA-cNGR was confirmed in the Matrigel model and, moreover, binding was demonstrated in the infarcted myocardium and infarct border zone.ConclusionsOur newly designed and developed angiogenesis imaging probe 111In-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0081-7) contains supplementary material, which is available to authorized users.

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function with ECG-gated myocardial SPECT.

123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n = 56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n = 36) had OR times of less than one month and had conservative medical therapy, and Group C (n = 38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS program LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r = -0.68 and -0.76, respectively). The delta severity scores (BMIPP scores - sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6 +/- 3.0 vs. 1.5 +/- 1.7 and 1.0 +/- 1.4, p < 0.001 ). The rate of dysfunctional segments with normal sestamihi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p < 0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.

Prognostic Value of Rest Tl-201/Dipyridamole Stress Tc-99m-MIBI Myocardial Single Photon Emission Computed Tomography (SPECT)

Background and Objectives:Dual isotope myocardial SPECT, rest thallium-201/dipyridamole stress Tc-99m sestamibi is used to diagnose coronary artery disease. We examined predictive value of myocardial SPECT for the prognosis of patients having or suspected coronary artery disease. Materials and Method:We examined 692 patients referred for dipyridamole stress myocardial perfusion SPECT. Cardiac events (hard and soft events were followed up with medical record review and telephone interview. Survival analysis and multivariate Cox proportional hazard model were used to find significant predictors and the incremental predictive value of myocardial SPECT. Patients with coronary angiography (n=246 were analyzed in separate group. Results: There were 4 hard events and 3 soft events in 341 normal SPECT group (1.20%/yr. There were 5 hard events and 21 soft events in 351 abnormal SPECT group (4.69%/yr. Survival curve was separated between normal SPECT group and abnormal SPECT group (p<0.01. In univariate analysis, smoking, history of myocardial infarction, typical chest pain and SPECT findings were important variables. In multivariate analysis, SPECT result was the single most independent predictor. Large reversible perfusion abnormality predicted worse prognosis. In patients with coronary angiography, SPECT did not add statistically significant predictive value to the coronary angiography. Conclusion:Dipyridamole stress Tl-201/ MIBI dual isotope myocardial perfusion SPECT provided excellent prognostic information. Extent of reversible perfusion decrease was the independent predictor of future cardiac events. (Korean Circulation J 1998;28(8 :1260-1271