Autologous bone marrow mononuclear cells labeled with Tc-99m hexamethylpropylene amine oxime scintigraphy after intracoronary stem cell therapy in acute myocardial infarction

Mesquita, Cláudio Tinoco; Corrêa, Patrícia Lavatori; Felix, R; Azevedo, Jader Cunha de; Alves, Susana P.; Oliveira, Carolina; Sousa, A; Borojević, Radovan; Dohmann, Hans Fernando Rocha

doi:10.1016/j.nuclcard.2005.05.010

Cited by 18 publications

(15 citation statements)

References 7 publications

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“…Our group has published a description of the first patient in this series 13 . An important characteristic of the studied routes was the large presence of labeled cells in other organs such as the lungs, probably due to the first-pass effect in organs related with hematopoiesis and lymphopoiesis, such as the liver and the spleen.…”

Section: Discussionmentioning

confidence: 99%

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Moreira¹,

Haddad²,

Silva³

et al. 2011

Arq. Bras. Cardiol.

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Section: Discussionmentioning

confidence: 99%

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Moreira¹,

Haddad²,

Silva³

et al. 2011

Arq. Bras. Cardiol.

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“…Pilot studies suggested that selected BM CD34 + cells might exhibit higher engraftment capacity than nonselected BM mononuclear cells. 5,6 Nevertheless, animal and human studies with labeled progenitor cells have thus far included 1 to a maximum of 8 subjects with recent MI, [6][7][8][9][10][11][12][13] precluding any meaningful systematic analysis of the potential relationship between the extent of myocardial injury and cell uptake. On the contrary, pivotal clinical studies have used LVEF (typically ≤45%) as the main inclusion criterion and efficacy end point 5,6 in the absence of any evidence that cell uptake is related to the degree of LVEF impairment.…”

Section: Clinical Perspective On P 328mentioning

confidence: 99%

Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone

Musiałek

Tekieli

Kostkiewicz

et al. 2013

Circ: Cardiovascular Imaging

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Background-Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34 + cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size.Methods and Results-Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary interventiontreated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/mL [limits, 58-356 ng/mL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7-12), 4.3×10 6 (0.7-9.9×10 6 ) 99m Tc-extametazime-labeled autologous bone marrow CD34 + cells (activity, MBq]) were administered transcoronarily (left anterior descending coronary artery).99m Tc-methoxyisobutyl isonitrile (99 m Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2-11) (of 17) segments with definitely abnormal/ absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4-45.9 g), and infarct border zone mass was 29.8 g (3.9-60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%-9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) but not with echocardiography LVEF (r=-0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=-0.28, P=0.16. The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=−0.38; P=0.04). Conclusions-This largest human study with labeled bone marrow CD34+ cell transcoronary transplantation after recent STsegment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone. (Circ Cardiovasc Imaging. 2013;6:320-328.) Key Words: cardiac magnetic resonance imaging ◼ CD34 + cells ◼ gadolinium late-enhancement ◼ infarct border zone ◼ myocardial infarction-cellular therapy ◼ progenitor cell tracking ◼ single-photon emission computed tomography ◼ transcoronary cell transplantation © 2012 American Heart Association, Inc. P rogenitor cell therapy is emerging as a promising therapeutic modality in patients with acute myocardial infarction (MI) and substantial myocardial injury, and over the la...

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“…Following uptake into cells, 18 FDG is phosphorylated by hexokinase, thus trapped within the labeled cells, permitting the detection using PET. Similarly, direct cell labeling with 111 indium-oxine (3) or 99m Tc-hexamethylpropylenamine oxime (52) has been used in conjunction with SPEC, and copper-64-pyruvaldehyde-bis (N 4 -methylthiosemicarbazone) (2) or 18 FDG (8) with PET for tracking various cell types following transplantation. When compared with MRI, PET and SPECT have significantly higher sensitivity despite a lower spatial resolution.…”

Section: Molecular Imaging For the Survival And Kinetics Of Engraftedmentioning

confidence: 99%

“…However, a major concern of using radioactive labeling is radiation exposure (16), which may inhibit cell viability and differentiation. A recent study in a rat model of MI demonstrated significant reduced proliferation and function of 99m Tc-hexamethylpropylenamine oxime-labeled human hematopoetic progenitor cells despite accurate homing to the infarcted myocardium (52). Another problem lies in the short half-life of the radiotracer, which may limit the duration for long-term cell tracking (a couple of hours in the case of 18 FDG and a few days in the case of 111 In and 64 Cu).…”

Section: Molecular Imaging For the Survival And Kinetics Of Engraftedmentioning

confidence: 99%

Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease

Fan

Cao

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Yu Q, Fan W, Cao F. Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease. Am J Physiol Heart Circ Physiol 305: H947-H959, 2013. First published July 26, 2013 doi:10.1152/ajpheart.00092.2013.-Cell-based myocardial regeneration has emerged as a promising therapeutic option for ischemic heart disease, though not yet at the level of routine clinical utility. Despite the encouraging results from initial preclinical studies that have demonstrated improved function and reduced infarct size of the ischemic myocardium following several candidate cell transplantation, the beneficial effects and molecular mechanisms of cardiac cell therapy are still unclear in clinical applications to date, and much remains to be optimized. To improve engraftment, accurate methods are required for tracking cell fate and quantifying functional outcome. In the present review, we summarized the current status and challenges of cardiac cell therapy for ischemic heart disease and discussed the strengths and limitations of currently available in vivo imaging techniques with special focus on the newly developed multimodality approaches for assessing the efficacy of engrafted donor cells. We also addressed the hurdles these imaging modalities are facing, including issues regarding immunogenicity and tumorigenicity of transplanted stem cells, and provided some the future perspectives on stem cell imaging. molecular imaging; stem cell therapy; ischemic heart disease THIS ARTICLE is part of a collection on Physiological Basis of Cardiovascular Cell and Gene Therapies. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology. org/.

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Autologous bone marrow mononuclear cells labeled with Tc-99m hexamethylpropylene amine oxime scintigraphy after intracoronary stem cell therapy in acute myocardial infarction

Cited by 18 publications

References 7 publications

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone

Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease

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Autologous bone marrow mononuclear cells labeled with Tc-99m hexamethylpropylene amine oxime scintigraphy after intracoronary stem cell therapy in acute myocardial infarction

Cited by 18 publications

References 7 publications

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação

Infarct Size Determines Myocardial Uptake of CD34 + Cells in the Peri-Infarct Zone

Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease

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Infarct Size Determines Myocardial Uptake of CD34 ⁺ Cells in the Peri-Infarct Zone