PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide
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PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide. / Nielsen, Carsten Haagen; Kimura, Richard H; Withofs, Nadia; Tran, Phuoc T; Miao, Zheng; Cochran, Jennifer R; Cheng, Zhen; Felsher, Dean; Kjær, Andreas; Willmann, Juergen K; Gambhir, Sanjiv S.
In: Cancer Research, Vol. 70, No. 22, 2010, p. 9022-30.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide
AU - Nielsen, Carsten Haagen
AU - Kimura, Richard H
AU - Withofs, Nadia
AU - Tran, Phuoc T
AU - Miao, Zheng
AU - Cochran, Jennifer R
AU - Cheng, Zhen
AU - Felsher, Dean
AU - Kjær, Andreas
AU - Willmann, Juergen K
AU - Gambhir, Sanjiv S
N1 - Copyright © 2010 AACR.
PY - 2010
Y1 - 2010
N2 - Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel 64Cu-1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard 18F-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both 64Cu-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the 64Cu-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01±0.61 versus 4.36±0.68; P
AB - Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel 64Cu-1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard 18F-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both 64Cu-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the 64Cu-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01±0.61 versus 4.36±0.68; P
KW - Animals
KW - Antigens, CD31
KW - Copper Radioisotopes
KW - Cystine-Knot Miniproteins
KW - Fluorescent Antibody Technique
KW - Integrins
KW - Mice
KW - Mice, Transgenic
KW - Mutation
KW - Neoplasms
KW - Neovascularization, Pathologic
KW - Positron-Emission Tomography
KW - Proto-Oncogene Proteins c-myc
KW - Proto-Oncogene Proteins p21(ras)
KW - Radiopharmaceuticals
KW - Sensitivity and Specificity
KW - Tissue Distribution
KW - Tomography, X-Ray Computed
U2 - 10.1158/0008-5472.CAN-10-1338
DO - 10.1158/0008-5472.CAN-10-1338
M3 - Journal article
C2 - 21062977
VL - 70
SP - 9022
EP - 9030
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 22
ER -
ID: 32982663