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Am J Nucl Med Mol Imaging 2012;2(1):99-109
Original Article
Non-invasive longitudinal imaging of tumor progression using an 111Indium
labeled CXCR4 peptide antagonist
Tessa Buckle, Nynke S van den Berg, Joeri Kuil, Anton Bunschoten, Joppe Oldenburg, Alexander D Borowsky, Jelle Wesseling, Ryo
Masada, Shinya Oishi, Nobutaka Fujii, Fijs WB van Leeuwen
Departments of Radiology and Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital (NKI-AvL),
Amsterdam, The Netherlands; Department of Radiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands;
Department of Pathology and Laboratory Medicine, Center for Comparative Medicine, School of Medicine, University of California at
Davis, Sacramento, USA; Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital (NKI-AvL),
Amsterdam, The Netherlands; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Received October 28, 2011; accepted November 5, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence,
CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The
indium labeled CXCR4 peptide-antagonist, 111In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary
intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development was
longitudinally monitored using SPET/CT and tracer uptake was compared to uptake in control lesions. Expression of CXCR4 was
validated using immunohistochemistry and flow cytometric analysis. The uptake of 111In-DTPA-Ac-TZ14011 was related to tumor
angiogenesis using 111In-c[RGDfK]-DTPA. Twenty four hours after tracer injection, MIN-O lesions could be discriminated from low
CXCR4-expressing control tumors, while the degree of angiogenesis based on the αvβ3 integrin expression in both tumor types was
similar. The uptake of 111In-DTPA-Ac-TZ14011 in early MIN-O lesions was significantly lower than in larger intermediate and late-
stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively. Intermediate and late stage lesions show a
higher degree of membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis. From this study we can
conclude that 111In-DTPA-Ac-TZ14011 can be used to visualize the CXCR4-expression in MIN-O lesions longitudinally.
(ajnmmi1110003).
Keywords: Chemokine receptor 4 (CXCR4), Ductal carcinoma in situ (DCIS), single photon emission computed tomography
(SPECT), mouse model, tumor progression, longitudinal imaging
Full text PDF
Address all correspondence to:
Dr. Fijs WB van Leeuwen
Department of Radiology
Interventional Molecular Imaging
Leiden University Medical Center (LUMC)
Leiden, The Netherlands.
E-mail: F.W.B.van_Leeuwen@lumc.nl
Original Article
Non-invasive longitudinal imaging of tumor progression using an 111Indium
labeled CXCR4 peptide antagonist
Tessa Buckle, Nynke S van den Berg, Joeri Kuil, Anton Bunschoten, Joppe Oldenburg, Alexander D Borowsky, Jelle Wesseling, Ryo
Masada, Shinya Oishi, Nobutaka Fujii, Fijs WB van Leeuwen
Departments of Radiology and Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital (NKI-AvL),
Amsterdam, The Netherlands; Department of Radiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands;
Department of Pathology and Laboratory Medicine, Center for Comparative Medicine, School of Medicine, University of California at
Davis, Sacramento, USA; Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital (NKI-AvL),
Amsterdam, The Netherlands; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Received October 28, 2011; accepted November 5, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence,
CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The
indium labeled CXCR4 peptide-antagonist, 111In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary
intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development was
longitudinally monitored using SPET/CT and tracer uptake was compared to uptake in control lesions. Expression of CXCR4 was
validated using immunohistochemistry and flow cytometric analysis. The uptake of 111In-DTPA-Ac-TZ14011 was related to tumor
angiogenesis using 111In-c[RGDfK]-DTPA. Twenty four hours after tracer injection, MIN-O lesions could be discriminated from low
CXCR4-expressing control tumors, while the degree of angiogenesis based on the αvβ3 integrin expression in both tumor types was
similar. The uptake of 111In-DTPA-Ac-TZ14011 in early MIN-O lesions was significantly lower than in larger intermediate and late-
stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively. Intermediate and late stage lesions show a
higher degree of membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis. From this study we can
conclude that 111In-DTPA-Ac-TZ14011 can be used to visualize the CXCR4-expression in MIN-O lesions longitudinally.
(ajnmmi1110003).
Keywords: Chemokine receptor 4 (CXCR4), Ductal carcinoma in situ (DCIS), single photon emission computed tomography
(SPECT), mouse model, tumor progression, longitudinal imaging
Full text PDF
Address all correspondence to:
Dr. Fijs WB van Leeuwen
Department of Radiology
Interventional Molecular Imaging
Leiden University Medical Center (LUMC)
Leiden, The Netherlands.
E-mail: F.W.B.van_Leeuwen@lumc.nl
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