Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart

Takahiro Higuchi, Martina Anton, Katja Dumler, Stefan Seidl, Jaroslav Pelisek, Antti Saraste, Andrea Welling, Franz Hofmann, Robert A.J. Oostendorp, Bernd Gansbacher, Stephan G. Nekolla, Frank M. Bengel, Rene M. Botnar, Markus Schwaiger

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1088-1094
Number of pages7
JournalJournal of Nuclear Medicine
Volume50
Issue number7
DOIs
Publication statusPublished - Jul 1 2009
Externally publishedYes

Fingerprint

Reporter Genes
Survival
Cell Survival
Iron
Cell Transplantation
Transplantation
Nude Rats
Injections
Feasibility Studies
Heart Transplantation
Biotin
Cell- and Tissue-Based Therapy
Fetal Blood
Phagocytosis
Endothelial Progenitor Cells
ferric oxide
Myocardium
Cell Count
Macrophages
Apoptosis

Keywords

  • Cardiology
  • Cell transplantation
  • Gene expression imaging
  • MRI
  • NIS
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart. / Higuchi, Takahiro; Anton, Martina; Dumler, Katja; Seidl, Stefan; Pelisek, Jaroslav; Saraste, Antti; Welling, Andrea; Hofmann, Franz; Oostendorp, Robert A.J.; Gansbacher, Bernd; Nekolla, Stephan G.; Bengel, Frank M.; Botnar, Rene M.; Schwaiger, Markus.

In: Journal of Nuclear Medicine, Vol. 50, No. 7, 01.07.2009, p. 1088-1094.

Research output: Contribution to journalArticle

Higuchi, T, Anton, M, Dumler, K, Seidl, S, Pelisek, J, Saraste, A, Welling, A, Hofmann, F, Oostendorp, RAJ, Gansbacher, B, Nekolla, SG, Bengel, FM, Botnar, RM & Schwaiger, M 2009, 'Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart', Journal of Nuclear Medicine, vol. 50, no. 7, pp. 1088-1094. https://doi.org/10.2967/jnumed.108.060665
Higuchi, Takahiro ; Anton, Martina ; Dumler, Katja ; Seidl, Stefan ; Pelisek, Jaroslav ; Saraste, Antti ; Welling, Andrea ; Hofmann, Franz ; Oostendorp, Robert A.J. ; Gansbacher, Bernd ; Nekolla, Stephan G. ; Bengel, Frank M. ; Botnar, Rene M. ; Schwaiger, Markus. / Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart. In: Journal of Nuclear Medicine. 2009 ; Vol. 50, No. 7. pp. 1088-1094.
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AU - Saraste, Antti

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AU - Hofmann, Franz

AU - Oostendorp, Robert A.J.

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