Imaging Integrin αvβ3 on Blood Vessels with 111In-RGD2 in Head and Neck Tumor Xenografts
SourceThe Journal of Nuclear Medicine (1978), 55, 2, (2014), pp. 281-6
Article / Letter to editor
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The Journal of Nuclear Medicine (1978)
SubjectRadboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 2: Cancer development and immune defence RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences
Arginine-glycine-aspartic acid (RGD)-based imaging tracers allow specific imaging of integrin alphavbeta3, a protein overexpressed during angiogenesis, leading to the possibility that it might serve as a tool to stratify patients for antiangiogenic treatment. However, these tracers have generally been characterized in xenograft models in which integrin alphavbeta3 was constitutively expressed by the tumor cells themselves. In the studies presented here, the use of (111)In-RGD2 as a tracer to image only integrin alphavbeta3 expression on blood vessels in the tumor was determined using tumor xenografts in which tumor cells were integrin alphavbeta3-negative. METHODS: DOTA-E-[c(RGDfK)]2 was radiolabeled with (111)In ((111)In-RGD2), and biodistribution studies were performed in squamous cell carcinoma of the head and neck (HNSCC) xenograft mouse models to determine the optimal peptide dose to image angiogenesis. Next, biodistribution and imaging studies were performed at the optimal peptide dose in 3 HNSCC mouse models, FaDu, SCCNij3, and SCCNij202. Immunohistochemical analysis of tumor vascular and cell surface expression of integrin alphavbeta3 and correlation analysis of vascular integrin alphavbeta3 and autoradiography were completed. RESULTS: All 3 HNSCC xenografts expressed integrin alphavbeta3 on the vessels only. The optimal peptide dose of (111)In-RGD2 was 1 mug or less for specific integrin alphavbeta3-mediated uptake of the tracer. SPECT/CT imaging showed clear uptake of the tracer in the periphery of the tumors, corresponding with well-vascularized areas of the tumor. Within the tumor, (111)In-RGD2 autoradiography coincided with vascular integrin alphavbeta3 expression, as determined immunohistochemically. Integrin alphavbeta3-mediated uptake was also detected in nontumor tissues, which, through immunohistochemical analysis, proved positive for integrin alphavbeta3. CONCLUSION: (111)In-RGD2 allows the visualization of integrin alphavbeta3 in xenograft models in which integrin alphavbeta3 is expressed only on the neovasculature, such as in the HNSCC tumors. Thus, (111)In-RGD2 allows specific visualization of angiogenesis in tumor models lacking constitutive tumoral integrin alphavbeta3 expression but may be less useful for this purpose in many tumors in which tumor cells express integrin alphavbeta3.
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