JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

First published online June 12, 2009, 10.2967/jnumed.108.060665
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
jnumed.108.060665v1
50/7/1088    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in JNM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Higuchi, T.
Right arrow Articles by Schwaiger, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Higuchi, T.
Right arrow Articles by Schwaiger, M.
Journal of Nuclear Medicine Vol. 50 No. 7 1088-1094
© 2009 by Society of Nuclear Medicine
doi: 10.2967/jnumed.108.060665

Basic Science Investigation

Combined Reporter Gene PET and Iron Oxide MRI for Monitoring Survival and Localization of Transplanted Cells in the Rat Heart

Takahiro Higuchi*,1, Martina Anton*,2, Katja Dumler2, Stefan Seidl3, Jaroslav Pelisek4, Antti Saraste1, Andrea Welling5, Franz Hofmann5, Robert A.J. Oostendorp6, Bernd Gansbacher2, Stephan G. Nekolla1, Frank M. Bengel1, Rene M. Botnar1 and Markus Schwaiger1

1 Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany; 2 Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Munich, Germany; 3 Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Munich, Germany; 4 Abteilung für Gefässchirurgie, Technische Universität München, Munich, Germany; 5 Institut für Pharmakologie und Toxikologie, Technische Universität München, Munich, Germany; and 6 III. Medizinische Klinik und Poliklinik Klinikum rechts der Isar, Technische Universität München, Munich, Germany

Correspondence: For correspondence or reprints contact: Takahiro Higuchi, Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Klinikum rechts der Isar Ismaninger, Strasse 22, 81675 Munich, Germany. E-mail: higuchi{at}po2.nsknet.or.jp

There is a need for in vivo monitoring of cell engraftment and survival after cardiac cell transplantation therapy. This study assessed the feasibility and usefulness of combined PET and MRI for monitoring cell engraftment and survival after cell transplantation. Methods: Human endothelial progenitor cells (HEPCs), derived from CD34+ mononuclear cells of umbilical cord blood, were retrovirally transduced with the sodium iodide symporter (NIS) gene for reporter gene imaging by 124I-PET and labeled with iron oxides for visualization by MRI. Imaging and histologic analysis were performed on 3 groups of nude rats on days 1, 3, and 7 after intramyocardial injection of 4 million HEPCs. Results: In vitro studies demonstrated stable expression of functional NIS protein and normal viability of HEPCs after transduction. On day 1, after intramyocardial transplantation, iron- and NIS-labeled HEPCs were visualized successfully on MRI as a regional signal void in the healthy myocardium and on PET as 124I accumulation. The 124I uptake decreased on day 3 and was undetectable on day 7, and the MRI signal remained unchanged throughout the follow-up period. Histologic analysis with CD31 and CD68 antibodies confirmed the presence of either labeled or nonlabeled control transplanted HEPCs at the site of injection on day 1 but not on day 7, when only iron-loaded macrophages were seen. Furthermore, deoxyuride-5'-triphosphate biotin nick end labeling showed extensive apoptosis at the site of transplantation. Conclusion: The combination of MRI and PET allows imaging of localization and survival of transplanted HEPCs together with morphologic information about the heart. Although iron labeling rapidly loses specificity for cell viability because of phagocytosis of iron particles released from dead cells, reporter gene expression provided specific information on the number of surviving cells. This multimodality approach allows complementary analysis of cell localization and viability.

Key Words: cardiology • PET • MRI • NIS • cell transplantation • gene expression imaging

* Contributed equally to this work.

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.


Related articles in JNM:

This Month in JNM

JNM 2009 50: 11A-12A. [Full Text]  



This article has been cited by other articles:


Home page
 JNMHome page
T. Higuchi, M. Anton, A. Saraste, K. Dumler, J. Pelisek, S. G. Nekolla, F. M. Bengel, and M. Schwaiger
Reporter Gene PET for Monitoring Survival of Transplanted Endothelial Progenitor Cells in the Rat Heart After Pretreatment with VEGF and Atorvastatin
J. Nucl. Med., November 1, 2009; 50(11): 1881 - 1886.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY THE JOURNAL OF NUCLEAR MEDICINE
Copyright © 2009 by the Society of Nuclear Medicine.