indium-oxine and Myocardial-Infarction

Topics: Blood Platelets; Coronary Thrombosis; Humans; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radiography; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated.. With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI.. Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Topics: Animals; Cell Differentiation; Cell Division; Cell Survival; Dogs; Indium Radioisotopes; Injections, Intravenous; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Reproducibility of Results; Stem Cells; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Transplantation, Homologous

Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.. Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.. The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Topics: Animals; Cell Lineage; Cell Movement; Cell Survival; Cell Transplantation; Clinical Trials as Topic; Coronary Vessels; Female; Graft Survival; Humans; Infusions, Intravenous; Injections, Intramuscular; Kidney; Leukocytes, Mononuclear; Liver; Lung; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Organometallic Compounds; Oxyquinoline; Radiopharmaceuticals; Random Allocation; Reproducibility of Results; Research Design; Spleen; Sus scrofa; Tissue Distribution; Transplantation, Heterologous

Transplantation of progenitor cells (PCs) has been shown to improve neovascularization and left ventricular function after myocardial ischemia. The fate of transplanted PCs has been monitored by fluorescence labeling or by genetic modifications introducing reporter genes. However, these techniques are limited by the need to kill the experimental animal. The aim of this study was to radiolabel CD34(+) hematopoietic PCs (HPCs) with (111)In-oxine and to evaluate the feasibility of this in vivo method for monitoring myocardial homing of transplanted cells in a rat myocardial infarction model.. Human HPCs were isolated from mobilized peripheral blood and labeled with (111)In-oxine. Labeled HPCs were injected into the cavity of the left ventricle in nude rats 24 h after induction of myocardial infarction (n = 4) or sham operation (n = 4). Scintigraphic images were acquired up to 96 h after HPC injection. After animals were killed, tissue samples of various organs were harvested to calculate tissue-specific activity and for immunostaining.. Labeling efficiency of HPCs was 32% +/- 11%. According to trypan-blue staining, viability of radiolabeled HPCs was impaired by 30% after 48 and 96 h in comparison with unlabeled cells, whereas proliferation and differentiation of HPCs was nullified after 7 d, as assessed by colony-forming assays. After injection of HPCs, the specific activity ratio of heart to peripheral muscle tissue increased from 1.10 +/- 0.32 in sham-operated rats to 2.47 +/- 0.92 (P = 0.020) in infarcted rats. However, the overall radioactivity detected in the heart was only about 1%. A transient high lung uptake of 17% +/- 6% was observed within the first hour after infusion of HPCs. At 24 h after injection, the initial lung activity had shifted toward liver, kidneys, and spleen, resulting in an increase of radioactivity in these organs from 37% +/- 6% to 57% +/- 5%.. Radiolabeling with (111)In-oxine is a feasible in vivo method for monitoring transplanted HPCs in a rat myocardial infarction model. The potential to detect differences in myocardial homing between infarcted and normal hearts suggests that this method may provide a noninvasive imaging approach for clinical trials using transplanted HPCs in patients. Our findings, however, also demonstrated a negative effect of (111)In-oxine on cellular function, which resulted in complete impairment of HPC proliferation and differentiation. For future trials in stem cell imaging with (111)In-oxine, therefore, it will be mandatory to carefully check for radiation-induced cell damage.

Topics: Animals; Antigens, CD34; Disease Models, Animal; Feasibility Studies; Female; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Isotope Labeling; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Nude; Treatment Outcome

Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs.. Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [111In]indium oxine. EPCs (106) were injected in athymic nude rats 24 hours after myocardial infarction (n=8) or sham operation (n=8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, approximately 70% of the radioactivity was localized in the spleen and liver, with only approximately 1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02+/-0.19 in sham-operated animals to 2.03+/-0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69+/-1.54 in sham-operated animals to 4.70+/-1.55 (P<0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone.. Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy.

Topics: Animals; Cells, Cultured; Endothelium, Vascular; Female; Fluorescence; Fluorescent Antibody Technique; Heart Ventricles; Humans; Indium Radioisotopes; Injections; Injections, Intravenous; Lipoproteins, LDL; Myocardial Infarction; Myocardium; Organometallic Compounds; Oxyquinoline; Rats; Rats, Nude; Stem Cell Transplantation; Tissue Distribution

Coronary arteriography revealed significant left anterior descending coronary artery stenosis in a 72-year-old man with a history of myocardial infarction. Stenting of the stenotic vessel was performed. Twelve hours after stenting the patient complained of chest pain but emergent coronary arteriography did not show sign of any coronary arterial stenosis. Under suspicion of coronary thrombus formation, indium-111-oxine-labeled platelet scintigraphy was performed 5 days after stenting, and revealed accumulation of indium-111-oxine in the area corresponding to the stent implantation site.

Topics: Aged; Blood Platelets; Coronary Angiography; Coronary Disease; Humans; Indium Radioisotopes; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Platelet Aggregation Inhibitors; Radionuclide Imaging; Stents

The diagnosis of post myocardial infarction syndrome (PMIS) is sometimes difficult because of the absence of a specific test. We report a 68-year-old man with PMIS who had a persistent accumulation of indium-111 oxine labeled leukocytes in the infarcted myocardium for 1 month. The uptake of leukocytes preceded the appearance of the main symptoms and disappeared with the clinical improvement after the therapy with steroids. Leukocyte imaging has a potential as a useful tool for early diagnosis, evaluation of therapy and assessing the mechanism of PMIS.

Topics: Aged; Humans; Indium Radioisotopes; Leukocytes; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Syndrome; Tomography, Emission-Computed, Single-Photon

Autologous 111In oxine-labelled platelet scintigraphy was used to detect left ventricular thrombi in 20 patients with anterior and 18 patients with inferior Q wave myocardial infarction within 48-72 h. Left ventricular thrombi were found in 8/20 patients with anterior myocardial infarction and in 1/18 patients with inferior myocardial infarction, giving a total incidence of 24%. Patients with left ventricular thrombi were older (64.3 versus 58.2 years), had higher peak creatinine kinase (CK) levels (4523 versus 2749 IU 1-1), lower ejection fraction (19.5 versus 37.8%, P less than 0.005) and were more likely to have an enlarged left ventricle than those without left ventricular thrombi (87.5 versus 54.5%, P less than 0.001). Left ventricular thrombi were found overlying sites of myocardial infarction in 8 out of 9 patients. Apical left ventricular thrombi were 1.7 times more common than septal left ventricular thrombi. All patients received minidose heparin for prevention of deep venous thrombosis. This technique is complementary to echocardiography and may provide additional information in the difficult cases where the decision about full-dose anticoagulation is in doubt.

Topics: Adult; Aged; Blood Platelets; Female; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Thrombosis

Intracardiac thrombi can be localized and quantified by indium-111-labelling of thrombocytes with a high sensitivity and specificity. The scintigraphic procedure has a complementary evidence to echocardiography. Scintigraphy shows activity and age of thrombosis, whereas echocardiography seems to be superior in determination of mass and localization. In older thrombi scintigraphy fails because of organisation and endothelialization of the thrombus surface. For the reason of determination of the age of an intraventricular thrombus this method might have an increasing acceptance.

Topics: Aged; Blood Platelets; Coronary Disease; Coronary Thrombosis; Humans; Indium Radioisotopes; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Prognosis; Radionuclide Imaging

Intracardiac thrombi can be localized and quantified by Indium-111-labelling of thrombocytes with a high sensitivity and specificity. The scintigraphic procedure has a complementary evidence to echocardiography. Scintigraphy shows activity and age of thrombosis, whereas echocardiography seems to be superior in determination of mass and localization. In older thrombi scintigraphy fails because of organisation and endothelialization of the thrombus surface. For the reason of determination of the age of an intraventricular thrombus this method might have an increasing acceptance.

Topics: Aged; Blood Platelets; Coronary Disease; Coronary Thrombosis; Heart Ventricles; Humans; Hydroxyquinolines; Indium Radioisotopes; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Recurrence

Eighteen patients with postinfarction left ventricular aneurysms (LVAs) were examined with Indium-111-labeled autologous platelet scintigraphy to identify intracardiac thrombi and to investigate the effect of antithrombotic agents on thrombogenesity within their LVAs. Left ventriculography (LVG), and two-dimensional echocardiography were also carried out to assess the diagnostic ability of the platelet imaging. Indium-111-platelet scintigraphy for the detection of LVA mural thrombi had a sensitivity of 60% and a specificity of 100%. Four of six patients with false-negative scintigraphic studies had been under antiplatelet therapy. Eight of the nine patients who had showed active platelet deposition on initial examination had not received antiplatelet therapy. Thereafter, five of these nine were treated with tichlopidine (300 mg/day) for 29.8 +/- 5.0 days. On the second platelet study, two had resolution and the other three had interruption of intra-aneurysmal deposition, which remained positive. In only one patient of the three, the third platelet study was performed after warfarin therapy. It took two weeks after beginning the therapy to completely interrupt platelet deposition within the LVA in this patient. ECG gated radionuclide ventriculography and Thallium-201-myocardial scintigraphy were also performed to assess left ventricular wall motion of left ventricular ejection fraction (LVEF) and myocardial blood perfusion. Thallium-201-SPECT showed apical or anteroapical perfusion defects and the radionuclide ventriculography correctly identified all 18 apical and anteroseptal aneurysms which were confirmed by LVG methods. The comparison between the thrombus positive group and the thrombus negative group was carried out on both the LVEF and the period from the last myocardial infarction to the initial platelet scanning study. There were no statistical differences in the LVEF and the interval (34.5 +/- 12.5% vs 37.3 +/- 14.6%, 39.6 +/- 52.6 days vs 89.6 +/- 108.3 days) between the two groups. These results suggest that Indium-111-labeled platelet scintigraphy can be a reliable method for the identification of active left ventricular mural thrombi and a practical method of judging antiplatelet and anticoagulant therapy.

Topics: Adult; Aged; Blood Platelets; Evaluation Studies as Topic; Heart Aneurysm; Humans; Hydroxyquinolines; Indium Radioisotopes; Male; Middle Aged; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Thrombosis

The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion.

Topics: Acute Disease; Acute-Phase Reaction; Female; Heart; Humans; Hydroxyquinolines; Indium; Inflammation; Liver; Male; Middle Aged; Myocardial Infarction; Neutrophils; Organometallic Compounds; Oxyquinoline; Radioisotopes; Spleen; Tomography, Emission-Computed

Intracardiac and arterial thrombi were examined by scintigraphy using In-111-oxine labeled autologous platelets. In 22 cases of myocardial infarction including six with ventricular aneurysms, four had positive findings of thrombi on imaging and detected also by echocardiography. All four had ventricular aneurysms. The so-called "moya-moya" echoes (fuzzy echoes) were demonstrated in two of these four cases. We encountered two cases with positive findings on imaging in 13 with mitral valve disease. These two had systemic embolic episodes after scintigraphic examination. "Moya-moya" echoes were detected in the left atrial cavity in four with negative findings on imaging. Positive images were obtained in two of three with acute arterial occlusive disease, and in both cases platelet deposition was observed in the proximal site of obstruction. Though thrombectomy was performed for one of these two cases, no thrombus was detected at the site of platelet deposition. After one month, re-examination revealed only negative findings in all sites in both these patients. In the six cases of aortic aneurysm, three had platelet deposition within their aneurysms, and surgery was performed for these positive cases, but one of them had no thrombus. Positive images were obtained in only one of seven patients with chronic arterial occlusive disease. Coagulation tests and platelet studies were investigated for patients with positive or negative platelet scans. Only the data of the thrombo-test showed a significant difference (97 +/- 9% vs 23 +/- 7%, p less than 0.001). Three cases of positive imaging became negative after anticoagulant therapy. We tried ECT for eight cases 24 hours after injection of In-111-oxine labeled platelets. Three cases showed clear images of thrombi, while the planar images could not detect them at an early stage. Therefore, we propose that ECT can be a useful technique for diagnosing intracardiac thrombi in early stage.

Topics: Aged; Arterial Occlusive Diseases; Blood Platelets; Child; Child, Preschool; Heart Diseases; Humans; Hydroxyquinolines; Indium; Infant; Infant, Newborn; Male; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Thrombosis; Tomography, Emission-Computed

Since indium-111 platelet scintigraphy for the detection of left ventricular thrombosis often shows considerable non-specific blood pool activity a subtraction method using simultaneous technetium-99m blood pool scintigraphy was undertaken in 11 subjects with well documented remote myocardial infarction, who served as positive or negative controls, and in 18 consecutive patients with acute myocardial infarction. The results were compared with those of cross sectional echocardiography. Thirteen patients had transmural myocardial infarction and the calculated count per pixel in the left ventricle of the subtracted indium-111 platelet scintigram was (mean (SD)) 0.28(0.35), but five patients with subendocardial myocardial infarction had a mean count of 0.04(0.06). In seven patients with transmural myocardial infarction (two anterior and five inferior) left ventricular thrombosis was detected by indium-111 platelet scintigraphy but in only one of these by cross sectional echocardiography. None of the patients with subendocardial myocardial infarction had left ventricular thrombosis. Subtracted left ventricular counts correlated well with the visual results. It is concluded that left ventricular platelet sequestration after acute myocardial infarction may be quantified and precisely located and that quantitative longitudinal studies of the natural history and drug intervention are now possible.

Topics: Adult; Aged; Blood Platelets; Echocardiography; Female; Heart; Heart Ventricles; Humans; Hydroxyquinolines; Indium; Male; Middle Aged; Myocardial Infarction; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Subtraction Technique; Thrombosis