Image-guided, Tumor Stroma-targeted 131I Therapy of Hepatocellular Cancer After Systemic Mesenchymal Stem Cell-mediated NIS Gene Delivery

被引：71

作者：

Knoop, Kerstin ^{[1
]}

Kolokythas, Marie ^{[1
]}

Klutz, Kathrin ^{[1
]}

Willhauck, Michael J. ^{[1
]}

Wunderlich, Nathalie ^{[1
]}

Draganovici, Dan ^{[2
]}

Zach, Christian ^{[3
]}

Gildehaus, Franz-Josef ^{[3
]}

Boening, Guido ^{[3
]}

Goeke, Burkhard ^{[1
]}

Wagner, Ernst ^{[4
]}

Nelson, Peter J. ^{[2
]}

Spitzweg, Christine ^{[1
]}

机构：

[1] Univ Munich, Dept Internal Med 2, Munich, Germany

[2] Univ Munich, Med Policlin, Clin Biochem Grp, Munich, Germany

[3] Univ Munich, Dept Nucl Med, Munich, Germany

[4] Univ Munich, Dept Pharm, Ctr Drug Res Pharmaceut Biol Biotechnol, Munich, Germany

来源：

MOLECULAR THERAPY | 2011年 / 19卷 / 09期

关键词：

SODIUM-IODIDE SYMPORTER; POSITRON-EMISSION-TOMOGRAPHY; ENGINEERED MEASLES-VIRUS; PROSTATE-CANCER; IN-VIVO; RADIOIODINE THERAPY; NA/I SYMPORTER; REPORTER GENE; REPLICATING ADENOVIRUS; RADIONUCLIDE THERAPY;

D O I：

10.1038/mt.2011.93

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Due to its dual role as reporter and therapy gene, the sodium iodide symporter (NIS) allows noninvasive imaging of functional NIS expression by I-123-scintigraphy or I-124-PET imaging before the application of a therapeutic dose of I-131. NIS expression provides a novel mechanism for the evaluation of mesenchymal stem cells (MSCs) as gene delivery vehicles for tumor therapy. In the current study, we stably transfected bone marrow-derived CD34(-) MSCs with NIS cDNA (NIS-MSC), which revealed high levels of functional NIS protein expression. In mixed populations of NIS-MSCs and hepatocellular cancer (HCC) cells, clonogenic assays showed a 55% reduction of HCC cell survival after I-131 application. We then investigated body distribution of NIS-MSCs by I-123-scintigraphy and I-124-PET imaging following intravenous (i.v.) injection of NIS-MSCs in a HCC xenograft mouse model demonstrating active MSC recruitment into the tumor stroma which was confirmed by immunohistochemistry and ex vivo gamma-counter analysis. Three cycles of systemic MSC-mediated NIS gene delivery followed by I-131 application resulted in a significant delay in tumor growth. Our results demonstrate tumor-specific accumulation and therapeutic efficacy of radioiodine after MSC-mediated NIS gene delivery in HCC tumors, opening the prospect of NIS-mediated radionuclide therapy of metastatic cancer using MSCs as gene delivery vehicles.

引用

页码：1704 / 1713

页数：10

共 49 条

[41] A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer [J].