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Mol Imaging Biol. 2011 Jun;13(3):526-535. doi: 10.1007/s11307-010-0375-0.

Evaluation of two internalizing carcinoembryonic antigen reporter genes for molecular imaging.

Author information

1
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Box 951770, 570 Westwood Plaza, Los Angeles, CA, 90095-1770, USA.
2
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Box 951770, 570 Westwood Plaza, Los Angeles, CA, 90095-1770, USA. awu@mednet.ucla.edu.

Abstract

PURPOSE:

The objective of this article is to develop internalizing positron emission tomography (PET) reporter genes for tracking genetically modified T cells in vivo.

PROCEDURES:

The transmembrane and cytoplasmic domains of the human transferrin receptor (TfR) and CD5 were each fused to the carcinoembryonic (CEA) minigene N-A3 and expressed in Jurkat T cells. Internalization was evaluated by confocal microscopy or by intracellular uptake of ¹²⁵I-labeled anti-CEA scFv-Fc. Reporter gene-transfected Jurkat xenografts in mice were analyzed by immunohistochemistry (IHC) and imaged by PET using ¹²⁴I- or ⁶⁴Cu-scFv-Fc as tracers.

RESULTS:

Surface expression of TR(1-99)-NA3 was lower than that of NA3-CD5. Both reporter genes were internalized following binding of the anti-CEA antibody fragment. IHC of tumors showed strong staining of NA3-CD5, whereas TR(1-99)-NA3 stained weakly. Specific targeting of TR(1-99)-NA3 or NA3-CD5 was shown by PET in xenografted mice.

CONCLUSIONS:

The in vivo imaging studies suggest a potential application of the internalizing form of CEA (N-A3) as a PET reporter gene.

PMID:
20628903
PMCID:
PMC2992604
DOI:
10.1007/s11307-010-0375-0
[Indexed for MEDLINE]
Free PMC Article

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