Comparison of Cell-Labeling Methods with 124I-FIAU and 64Cu-PTSM for Cell Tracking Using Chronic Myelogenous Leukemia Cells Expressing HSV1-tk and Firefly Luciferase

Cell-tracking methods with molecular-imaging modality can monitor the biodistribution of cells. In this study, the direct-labeling method with Cu-64-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-64-PTSM), indirect cell-labeling methods with herpes simplex virus type 1-thymidine kinase (HSV1-tk)-mediated I-124-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (I-124-FIAU) were comparatively investigated in vitro and in vivo for tracking of human chronic myelogenous leukemia cells. K562-TL was established by retroviral transduction of the HSV1-tk and firefly luciferase gene in the K562 cell. K562-TL cells were labeled with Cu-64-PTSM or I-124-FIAU. Cell labeling efficiency, viability, and radiolabels retention were compared in vitro. The biodistribution of radiolabeled K562-TL cells with each radiolabel and small-animal positron emission tomography imaging were performed. Additionally, in vivo and ex vivo bioluminescence imaging (BLI) and tissue reverse transcriptase-polymerase chain reaction (RT-PCR) analysis were used for confirming those results. K562-TL cells were efficiently labeled with both radiolabels. The radiolabel retention (%) of I-124-FIAU (95.2% +/- 1.1%) was fourfold higher than Cu-64-PTSM (23.6% +/- 0.7%) at 24 hours postlabeling. Viability of radiolabeled cells was statistically nonsignificant between I-124-FIAU and Cu-64-PTSM. The radioactivity of each radiolabeled cells was predominantly accumulated in the lungs and liver at 2 hours. Both the radioactivity of Cu-64-PTSM- and I-124-FIAU-labeled cells was highly accumulated in the liver at 24 hours. However, the radioactivity of I-124-FIAU-labeled cells was markedly decreased from the body at 24 hours. The K562-TL cells were dominantly localized in the lungs and liver, which also verified by BLI and RT-PCR analysis at 2 and 24 hours postinjection. The Cu-64-PTSM-labeled cell-tracking method is more efficient than I-124-FIAU-labeled cell tracking, because of markedly decrease of radioactivity and fast efflux of I-124-FIAU in vivo. In spite of a high labeling yield and radiolabel retention of I-124-FIAU in vitro, the in vivo cell-tracking method using Cu-64-PTSM could be a useful method to evaluate the distribution and targeting of various cell types, especially, stem cells and immune cells.