Imaging integrin αvβ3 on blood vessels with 111In-RGD2 in head and neck tumor xenografts

Samantha Y A Terry, Keelara Abiraj, Cathelijne Frielink, Laura K van Dijk, Johan Bussink, Wim J Oyen, Otto C Boerman

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

UNLABELLED: Arginine-glycine-aspartic acid (RGD)-based imaging tracers allow specific imaging of integrin αvβ3, 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 αvβ3 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 αvβ3 expression on blood vessels in the tumor was determined using tumor xenografts in which tumor cells were integrin αvβ3-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 αvβ3 and correlation analysis of vascular integrin αvβ3 and autoradiography were completed.

RESULTS: All 3 HNSCC xenografts expressed integrin αvβ3 on the vessels only. The optimal peptide dose of (111)In-RGD2 was 1 μg or less for specific integrin αvβ3-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 αvβ3 expression, as determined immunohistochemically. Integrin αvβ3-mediated uptake was also detected in nontumor tissues, which, through immunohistochemical analysis, proved positive for integrin αvβ3.

CONCLUSION: (111)In-RGD2 allows the visualization of integrin αvβ3 in xenograft models in which integrin αvβ3 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 αvβ3 expression but may be less useful for this purpose in many tumors in which tumor cells express integrin αvβ3.

Original languageEnglish
Pages (from-to)281-6
Number of pages6
JournalJournal of Nuclear Medicine
Volume55
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Animals
  • Blood Vessels
  • Carcinoma, Squamous Cell
  • Cell Line, Tumor
  • Female
  • Head and Neck Neoplasms
  • Immunohistochemistry
  • Indium Radioisotopes
  • Integrin alphaVbeta3
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Oligopeptides
  • Radiopharmaceuticals
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed

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