In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 18; pp. 7315 - 7324
• Main Authors: Kim, Hoe Suk, Cho, Hye Rim, Choi, Seung Hong, Woo, Ji Su, Moon, Woo Kyung
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.2010
• Subjects: Animals; Antineoplastic agents; Apoferritins - biosynthesis; Apoferritins - genetics; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Genetic Vectors - genetics; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - genetics; Humans; Lentivirus - genetics; Magnetic Resonance Imaging - instrumentation; Magnetic Resonance Imaging - methods; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-myc - biosynthesis; Proto-Oncogene Proteins c-myc - genetics; Rats; Rats, Inbred F344; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Transduction, Genetic; Tumors; Human; Scanner; Magnetic resonance; Ferritin; Retroviridae; Malignant tumor; Nuclear magnetic resonance imaging; Lentivirus; Virus; In vivo; Signal transduction; Imaging; Green fluorescent protein; Medical imagery; Vector; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-10-0241

A combination of reporter genes for magnetic resonance imaging (MRI) and optical imaging can provide an additional level of noninvasive and quantitative information about biological processes occurring in deep tissues. We developed a bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc-tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging to detect green fluorescent protein (GFP) expression. The transgene construct was stably transfected into MCF-7 and F-98 cells. After transplantation of the cells expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence imaging were performed with a human wrist coil on a 1.5T MR scanner and optical imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc-hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining and iron binding assays. The myc-hFTH cells and tumors had significantly lower signal intensities in T(2)-weighted MRI than mock-transfected controls (P ≤ 0.05). This is direct evidence that myc-hFTH expression can be visualized noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and fluorescence imaging of transplanted cells at molecular and cellular levels can be performed simultaneously using our bimodal lentiviral vector system. Our techniques can be used to monitor tumor growth, metastasis, and regression during cell and gene-based therapy in deep tissues.