title: (18)F-FDG cell labeling may underestimate transplanted cell homing: more accurate, efficient, and stable cell labeling with hexadecyl-4-[(18)F]fluorobenzoate for in vivo tracking of transplanted human progenitor cells by positron emission tomography.
abstract: Cell therapy is expected to restore perfusion and improve function in the ischemic/infarcted myocardium; however, the biological mechanisms and local effects of transplanted cells remain unclear. To assess cell fate in vivo, hexadecyl-4-[(18)F]fluorobenzoate ((18)F-HFB)  cell labeling was evaluated for tracking human circulating progenitor cells (CPCs) with positron emission tomography (PET) and was compared to the commonly used 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) labeling method in a rat myocardial infarction model. CPCs were labeled  with 18F-HFB or (18)F-FDG ex vivo under the same conditions. (18)F-HFB cell-labeling efficiency (23.4 ± 7.5%) and stability (4 h, 88.4 ± 6.0%) were superior to (18)F-FDG (7.6 ± 4.1% and 26.6 ± 6.1%, respectively; p < 0.05). Neither  labeling approach significantly altered cell viability, phenotype or migration potential up to 24 h postlabeling. Two weeks after left anterior descending coronary artery ligation, rats received echo-guided intramyocardial injection in the infarct border zone with (18)F-HFB-CPCs,  (18)F-FDG-CPCs, (18)F-HFB, or (18)F-FDG. Dynamic PET imaging of both (18)F-HFB-CPCs and(18)F-FDG-CPCs demonstrated that only 16-37% of the initial injection dose (ID) was retained in the injection site at 10 min postdelivery, and remaining  activity fell significantly over the first 4 h posttransplantation. The (18)F-HFB-CPC signal in the target area at 2 h (23.7 ± 14.7% ID/g) and 4 h (17.6 ± 13.3% ID/g) postinjection was greater than that of (18)F-FDG-CPCs (5.4 ± 2.3% ID/g and 2.6 ±  0.7% ID/g, respectively;p < 0.05). Tissue biodistribution confirmed the higher radioactivity in the border zone of (18)F-HFB-CPC rats. Immunostaining of heart tissue sections revealed no significant difference in cell retention between two labeled cell transplantation groups.  Good correlation with biodistribution results was observed in the (18)F-HFB-CPC rats (r = 0.81, p < 0.05). Compared to (18)F-FDG, labeling human CPCs with(18)F-HFB provides a more efficient, stable, and accurate way to quantify the distribution of transplanted  cells. (18)F-HFB cell labeling with PET imaging offers a better modality to enhance our understanding of early retention, homing, and engraftment with cardiac cell therapy.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jean N
authors.initials: JN
authors.lastname: Dasilva
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Hadizad
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thorn
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Renaud
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Myra
authors.initials: M
authors.lastname: Kordos
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dekemp
authors.forename: Rob S
authors.initials: RS
authors.lastname: Beanlands
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
mesh_terms: D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000032:analysis* / Q000493:pharmacokinetics; D006801:Humans; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000601:surgery; D049268:Positron-Emission Tomography / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000000981:diagnostic imaging*; D014018:Tissue Distribution
chemical_list: D019788:Fluorodeoxyglucose F18