title: Infarct size determines myocardial uptake of CD34+ cells in the peri-infarct zone: results from a study of (99m)Tc-extametazime-labeled cell visualization integrated with cardiac magnetic resonance infarct imaging.
abstract: 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.
  
  
  RESULTS
  Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary intervention-treated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58-356 ng/dL]) 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, 77 MBq [45.9-86.7 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) and with peak troponin I (r=0.76, P<0.001); it also correlated with severely abnormal/absent perfusion segment number (r=0.45, P=0.008) and late gadolinium-enhanced infarct core (r=0.58 and r=0.84, P<0.0001) 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 ST-segment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.
authors.affiliation: Departments of Cardiac and Vascular Diseases, Jagiellonian University Institute of Cardiology, John Paul II Hospital, Krakow, Poland. pmusialek@szpitaljp2.krakow.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Musialek
authors.forename: Lukasz
authors.initials: L
authors.lastname: Tekieli
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kostkiewicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Miszalski-Jamka
authors.forename: Piotr
authors.initials: P
authors.lastname: Klimeczek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mazur
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szot
authors.forename: Marcin
authors.initials: M
authors.lastname: Majka
authors.forename: R Pawel
authors.initials: RP
authors.lastname: Banys
authors.forename: Danuta
authors.initials: D
authors.lastname: Jarocha
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Walter
authors.forename: Maciej
authors.initials: M
authors.lastname: Krupinski
authors.forename: Piotr
authors.initials: P
authors.lastname: Pieniazek
authors.forename: Maria
authors.initials: M
authors.lastname: Olszowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zmudka
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Pasowicz
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Tracz
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wojakowski
mesh_terms: D000328:Adult; D000368:Aged; D056988:Anterior Wall Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D062645:Percutaneous Coronary Intervention; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D020127:Recovery of Function; D013318:Stroke Volume; D019690:Technetium Tc 99m Exametazime; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D019275:Radiopharmaceuticals; D014336:Troponin; D019690:Technetium Tc 99m Exametazime