title: 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.
abstract: Cell-tracking methods with molecular-imaging modality can monitor the biodistribution of cells. In this study, the direct-labeling method with ⁶⁴Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (⁶⁴Cu-PTSM), indirect cell-labeling methods with herpes simplex virus type 1-thymidine kinase (HSV1-tk)-mediated ¹²⁴I-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil (¹²⁴I-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 ⁶⁴Cu-PTSM or ¹²⁴I-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 ¹²⁴I-FIAU (95.2%±1.1%) was fourfold higher than ⁶⁴Cu-PTSM (23.6%±0.7%) at 24 hours postlabeling. Viability of radiolabeled cells was statistically nonsignificant between ¹²⁴I-FIAU and ⁶⁴Cu-PTSM. The radioactivity of each radiolabeled cells was predominantly accumulated in the lungs and liver at 2 hours. Both the radioactivity of ⁶⁴Cu-PTSM- and ¹²⁴I-FIAU-labeled cells was highly accumulated in the liver at 24 hours. However, the radioactivity of ¹²⁴I-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 ⁶⁴Cu-PTSM-labeled cell-tracking method is more efficient than ¹²⁴I-FIAU-labeled cell tracking, because of markedly decrease of radioactivity and fast efflux of ¹²⁴I-FIAU in vivo. In spite of a high labeling yield and radiolabel retention of ¹²⁴I-FIAU in vitro, the in vivo cell-tracking method using ⁶⁴Cu-PTSM could be a useful method to evaluate the distribution and targeting of various cell types, especially, stem cells and immune cells.
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences-KIRAMS, Seoul, Republic of Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Park
authors.forename: Tae-Sup
authors.initials: TS
authors.lastname: Lee
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Son
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Chun
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Song
authors.forename: Yong-Serk
authors.initials: YS
authors.lastname: Park
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D058948:Cell Tracking / Q000379:methods; D003301:Copper Radioisotopes / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049409:Luciferases, Firefly / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D003301:Copper Radioisotopes; D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex; D001086:Arabinofuranosyluracil; C043457:fialuridine; D049409:Luciferases, Firefly; D013937:Thymidine Kinase