ACS Medicinal Chemistry Letters
Letter
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culating progenitor cells were noninvasively monitored in a rat
myocardial infarction model up to 4 h, but long-term
monitoring is impossible due to the short half-life of 18F.13
However, in the current study, we used 64Cu, which has a
relatively long half-life; thus, 1-labeled ADSCs were monitored
in vivo up to 18 h. Adonai et al. reported that a lipophilic agent,
64Cu-PTSM, was rapidly effluxed from C6 rat glioma cells;
radioactivity decreased by ∼80% at 24 h.3 Also, Park et al.
reported that radioactivity of intravenously injected 64Cu-
PTSM-labeled K562 (human erythromyeloblastoid leukemia
cell line) cells rapidly decreased in the lungs from 2 to 24 h.17
In the current results, however, the intramuscularly injected 1-
labeled ADSCs were clearly visualized at the injection site for
18 h.
Although we did not investigate the effect of 1-labeling on
the functionality of stem cells, through our previous study a
lipophilic labeling agent similar to 1, 124I-HIB, did not affect
stem cell differentiation including osteogenic, chondrogenic,
adipogenic, and cardiomyogenic lineage.18 Thus, labeling with 1
may not affect stem cell functionality.
(5) Huang, X.; Zhang, F.; Wang, H.; Niu, G.; Choi, K. Y.;
Swierczewska, M.; Zhang, G.; Gao, H.; Wang, Z.; Zhu, L.; Choi, H. S.;
Lee, S.; Chen, X. Mesenchymal stem cell-based cell engineering with
multifunctional mesoporous silica nanoparticles for tumor delivery.
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In conclusion, we have designed and synthesized 1, a PET
imaging agent, and evaluated the efficiency of monitoring
transplanted stem cells in normal rat heart. Compound 1 was
efficiently labeled with ADSCs, and 1-labeled ADSCs were
successfully monitored in vivo by PET imaging. Cell labeling
with 1 is a simple and suitable cell labeling agent for monitoring
of in vivo distribution and deposition of transplanted stem cells.
(10) Kato, K.; Umezawa, K.; Funeriu, D. P.; Miyake, M.; Miyake, J.;
Nagamune, T. Immobilized culture of nonadherent cells on an oleyl
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Silberberg, Y. R.; Rao, S. R.; Nakamura, C. Controlled cell adhesion
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(12) Ma, B.; Hankenson, K. D.; Dennis, J. E.; Caplan, A. I.;
Goldstein, S. A.; Kilbourn, M. R. A simple method for stem cell
labeling with fluorine 18. Nucl. Med. Biol. 2005, 32, 701−705.
(13) Zhang, Y.; Dasilva, J. N.; Hadizad, T.; Thorn, S.; Kuraitis, D.;
Renaud, J. M.; Ahmadi, A.; Kordos, M.; Dekemp, R. A.; Beanlands, R.
S.; Suuronen, E. J.; Ruel, M. 18F-FDG cell labeling may underestimate
transplanted cell homing: more accurate, efficient, and stable cell
labeling with hexadecyl-4-18F-fluorobenzoate for in vivo tracking of
transplanted human progenitor cells by positron emission tomography.
Cell Transplant. 2012, 21, 1821−1835.
(14) Barbash, I. M.; Chouraqui, P.; Baron, J.; Feinberg, M. S.; Etzion,
S.; Tessone, A.; Miller, L.; Guetta, E.; Zipori, D.; Kedes, L. H.; Kloner,
R. A.; Leor, J. Systemic delivery of bone marrow-derived mesenchymal
stem cells to the infarcted myocardium: feasibility, cell migration, and
body distribution. Circulation 2003, 108, 863−868.
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J.; Conget, P. A. Dynamics of distribution of human bone marrow-
derived mesenchymal stem cells after transplantation into adult
unconditioned mice. Transplantation 2004, 78, 503−508.
(16) Ma, B.; Hankenson, K. D.; Dennis, J. E.; Caplan, A. I.;
Goldstein, S. A.; Kilbourn, M. R. A simple method for stem cell
labeling with fluorine 18. Nucl. Med. Biol. 2005, 32, 701−705.
(17) Park, J. J.; Lee, T. S.; Son, J. J.; Chun, K. S.; Song, I. H.; Park, Y.
S.; Kim, K. I.; Lee, Y. J.; Kang, J. H. 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. Cancer Biother. Radiopharm. 2012, 27, 719−728.
(18) Kim, M. H.; Woo, S. K.; Lee, K. C.; An, G. I.; Pandya, D.; Park,
N. W.; Nahm, S. S.; Eom, K. D.; Kim, K. I.; Lee, T. S.; Kim, C. W.;
Kang, J. H.; Yoo, J.; Lee, Y. J. Longitudinal monitoring adipose-derived
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ASSOCIATED CONTENT
* Supporting Information
■
S
Detailed experimental procedures including synthesis, ADSCs
isolation, cell labeling with 1, small animal PET/CT imaging,
and digital whole-body autoradiography. This material is
AUTHOR INFORMATION
Corresponding Authors
■
Funding
This work was funded by the Nuclear R&D (grant code: NRF-
2012M2A2A7013480 and 2011-0030162) and Basic Science
Research (grant code: NRF-2012R1A1A2044945) Programs of
NRF, funded by MEST-Republic of Korea.
Notes
The authors declare no competing financial interest.
ABBREVIATIONS
■
ADSCs, adipose-derived stem cells; CT, computed tomog-
raphy; DOTA, 1,4,7,10-tetraazacyclododecane-tetraacetic acid;
HB, hexadecyl benzoate; PET, positron emission tomography;
TLC, thin layer chromatography
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