Noninvasive real-time imaging of tumors and metastases using tumor-targeting light-emitting Escherichia coli

被引:79
作者
Min, Jung-Joon [1 ]
Kim, Hyun-Ju [2 ]
Park, Jae Hyo [1 ]
Moon, Sungmin [1 ]
Jeong, Jae Ho [2 ]
Hong, Yeoung-Jin [2 ]
Cho, Kyoung-Oh [3 ]
Nam, Jong Hee [4 ]
Kim, Nacksung [5 ]
Park, Young-Kyu [6 ]
Bom, Hee-Seung [1 ]
Rhee, Joon Haeng [2 ]
Choy, Hyon E. [2 ]
机构
[1] Chonnam Natl Univ, Sch Med, Dept Nucl Med, Lab Vivo Mol Imaging, Kwangju, South Korea
[2] Chonnam Natl Univ, Sch Med, Dept Microbiol, Kwangju, South Korea
[3] Chonnam Natl Univ, Coll Vet Med, Dept Pathol, Kwangju, South Korea
[4] Chonnam Natl Univ, Sch Med, Dept Pathol, Kwangju, South Korea
[5] Chonnam Natl Univ, Sch Med, Dept Pharmacol, Kwangju, South Korea
[6] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea
关键词
tumor imaging; noninvasive small animal imaging; Escherichia coli; bacterial luciferase (Lux); green fluorescent protein (GFP); cancer-targeting bacteria;
D O I
10.1007/s11307-007-0120-5
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose: A number of bacteria types are known to preferentially grow in tumors. We have taken advantage of this phenomenon to target luciferase-expressing Escherichia coli to tumors and metastases in mouse models to image them noninvasively. Methods and Results: After intravenous injection of pLux-expressing E. coli (10(8) CFU), bioluminescence signals from the bacteria were detected exclusively in tumor tissue after 24 hours. The balanced-lethal host-vector system using the gene encoding aspartate beta-semialdehyde dehydrogenase (asd) enabled stable maintenance of the pLux in the tumor-targeting E. coli. This phenomenon of selective tumor targeting and proliferation of E. coli was observed in a diverse range of tumors implanted in nude mice. More importantly, E. coli was capable of targeting both primary tumors and metastases, enabling them to be imaged noninvasively in both nude and immunocompetent mice. Conclusions: Our results suggest the potential clinical use of this technology for tumor targeting.
引用
收藏
页码:54 / 61
页数:8
相关论文
共 32 条
[1]  
ASLAKSON CJ, 1992, CANCER RES, V52, P1399
[2]  
Baish JW, 2000, CANCER RES, V60, P3683
[3]  
Berman M.L, 1984, EXPERIMENTS GENE FUS
[4]   The complete genome sequence of Escherichia coli K-12 [J].
Blattner, FR ;
Plunkett, G ;
Bloch, CA ;
Perna, NT ;
Burland, V ;
Riley, M ;
ColladoVides, J ;
Glasner, JD ;
Rode, CK ;
Mayhew, GF ;
Gregor, J ;
Davis, NW ;
Kirkpatrick, HA ;
Goeden, MA ;
Rose, DJ ;
Mau, B ;
Shao, Y .
SCIENCE, 1997, 277 (5331) :1453-+
[5]   RECOMBINANT AVIRULENT SALMONELLA VACCINE STRAINS WITH STABLE MAINTENANCE AND HIGH-LEVEL EXPRESSION OF CLONED GENES INVIVO [J].
CURTISS, R ;
NAKAYAMA, K ;
KELLY, SM .
IMMUNOLOGICAL INVESTIGATIONS, 1989, 18 (1-4) :583-596
[6]   Combination bacteriolytic therapy for the treatment of experimental tumors [J].
Dang, LH ;
Bettegowda, C ;
Huso, DL ;
Kinzler, KW ;
Vogelstein, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :15155-15160
[7]   One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products [J].
Datsenko, KA ;
Wanner, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6640-6645
[8]  
Fox ME, 1996, GENE THER, V3, P173
[9]   CLONING AND CHARACTERIZATION OF THE ASD GENE OF SALMONELLA-TYPHIMURIUM - USE IN STABLE MAINTENANCE OF RECOMBINANT PLASMIDS IN SALMONELLA VACCINE STRAINS [J].
GALAN, JE ;
NAKAYAMA, K ;
CURTISS, R .
GENE, 1990, 94 (01) :29-35
[10]   Openings between defective endothelial cells explain tumor vessel leakiness [J].
Hashizume, H ;
Baluk, P ;
Morikawa, S ;
McLean, JW ;
Thurston, G ;
Roberge, S ;
Jain, RK ;
McDonald, DM .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (04) :1363-1380