Noninvasive positron emission tomography and fluorescence imaging of CD133+ tumor stem cells.
A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one of the best-characterized tumor stem cell markers for many intra- and extracranial tumor entities. Here we demonstrate the successful noninvasive detection of AC133(+) tumor stem cells by PET and near-infrared fluorescence molecular tomography in subcutaneous and orthotopic glioma xenografts using antibody-based tracers. Particularly, microPET with (64)Cu-NOTA-AC133 mAb yielded high-quality images with outstanding tumor-to-background contrast, clearly delineating subcutaneous tumor stem cell-derived xenografts from surrounding tissues. Intracerebral tumors as small as 2-3 mm also were clearly discernible, and the microPET images reflected the invasive growth pattern of orthotopic cancer stem cell-derived tumors with low density of AC133(+) cells. These data provide a basis for further preclinical and clinical use of the developed tracers for high-sensitivity and high-resolution monitoring of AC133(+) tumor stem cells.
Departments of Radiation Oncology, Nuclear Medicine, and Neurosurgery, University Hospital Freiburg, D-79106 Freiburg, Germany.
Simone
S
Gaedicke
Friederike
F
Braun
Shruthi
S
Prasad
Marcia
M
Machein
Elke
E
Firat
Michael
M
Hettich
Ravindra
R
Gudihal
Xuekai
X
Zhu
Kerstin
K
Klingner
Julia
J
Schüler
Christel C
CC
Herold-Mende
Anca-Ligia
AL
Grosu
Martin
M
Behe
Wolfgang
W
Weber
Helmut
H
Mäcke
Gabriele
G
Niedermann
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D005453:Fluorescence; D005909:Glioblastoma / Q000000981:diagnostic imaging; D006023:Glycoproteins / Q000276:immunology*; D064593:Heterografts; D051379:Mice; D064847:Multimodal Imaging; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D049268:Positron-Emission Tomography / Q000379:methods*; D014057:Tomography, X-Ray Computed
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse
CSCs; cancer stem cells; glioblastoma