111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model.
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Department of Nuclear Medicine, University Hospital Kiel, Kiel, Germany. winbren_2000@yahoo.com
Winfried
W
Brenner
Alexandra
A
Aicher
Thomas
T
Eckey
Schirin
S
Massoudi
Maaz
M
Zuhayra
Ulrike
U
Koehl
Christopher
C
Heeschen
Willm U
WU
Kampen
Andreas M
AM
Zeiher
Stefanie
S
Dimmeler
Eberhard
E
Henze
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007553:Isotope Labeling; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D016896:Treatment Outcome
D018952:Antigens, CD34; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C032950:indium oxine; D015125:Oxyquinoline