Reporter gene PET for monitoring survival of transplanted endothelial progenitor cells in the rat heart after pretreatment with VEGF and atorvastatin.
It has been suggested that vascular endothelial growth factor (VEGF) and statins enhance the survival, proliferation, and function of endothelial progenitor cells (EPCs). We investigated whether reporter gene PET can be used to detect the effects of atorvastatin and VEGF on survival of EPCs after transplantation in the rat heart.


METHODS
Healthy nude rats received an intramyocardial injection of 4 million human EPCs retrovirally transduced with the sodium/iodide symporter gene for reporter gene imaging. Reporter gene expression was imaged at days 1 and 3 after injection on a small-animal PET scanner with (124)I, and the presence of EPCs was confirmed by immunohistochemistry with human CD31 antibodies. The control group received EPCs transduced only with the reporter gene, whereas treatment groups received oral atorvastatin (10 mg/kg/d) and EPCs cotransduced with adenoviral vectors encoding VEGF in addition to sodium/iodide symporter.


RESULTS
Immunohistochemistry showed more EPCs at the site of injection after atorvastatin treatment and in the presence of VEGF expression in EPCs than in controls. PET successfully visualized EPCs as focal (124)I accumulation at the site of injection. The quantitative amount of (124)I accumulation assessed by PET was significantly higher in the pretreatment than control group. Autoradiography confirmed (124)I accumulation in the myocardium that correlated with the number of EPCs.


CONCLUSIONS
Early survival of transplanted EPCs in the rat myocardium is prolonged by pretreatment with a combination of atorvastatin and VEGF. Reporter gene PET, by successfully quantifying the effect, is an attractive tool for monitoring stem cell survival in vivo.
Higuchi
Takahiro
T
Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. higuchi@po2.nsknet.or.jp
Anton
Martina
M
Saraste
Antti
A
Dumler
Katja
K
Pelisek
Jaroslav
J
Nekolla
Stephan G
SG
Bengel
Frank M
FM
Schwaiger
Markus
M
D000818:Animals; D000069059:Atorvastatin; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology*; D017930:Genes, Reporter; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007267:Injections; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*
D006538:Heptanoic Acids; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000069059:Atorvastatin