title: Can 111In-RGD2 monitor response to therapy in head and neck tumor xenografts?
abstract: RGD (arginylglycylaspartic acid)-based imaging tracers allow specific imaging of integrin αvβ3 expression, proteins overexpressed during angiogenesis; however, few studies have investigated the potential of these tracers to monitor responses of antiangiogenic or radiation therapy. In the studies presented here, (111)In-RGD2 was assessed for its potential as an imaging tool to monitor such responses to therapies.
  
  
  METHODS
  DOTA-E-[c(RGDfK)]2 was radiolabeled with (111)In ((111)In-RGD2), and biodistribution studies were performed in mice with subcutaneous FaDu or SK-RC-52 xenografts after treatment with either antiangiogenic therapy (bevacizumab or sorafenib) or tumor irradiation (10 Gy). Micro-SPECT imaging studies and subsequent quantitative analysis were also performed. The effect of bevacizumab, sorafenib, or radiation therapy on tumor growth was determined.
  
  
  RESULTS
  The uptake of (111)In-RGD2 in tumors, as determined from biodistribution studies, correlated well with that quantified from micro-SPECT images, and both showed that 15 d after irradiation (111)In-RGD2 uptake was enhanced. Specific or nonspecific uptake of (111)In-RGD2 in FaDu or SK-RC-52 xenografts was not affected after antiangiogenic therapy, except in head and neck squamous cell carcinoma 19 d after the start of sorafenib therapy (P < 0.05). The uptake of (111)In-RGD2 followed tumor volume in studies featuring antiangiogenic therapy. However, the uptake of (111)In-RGD2 in FaDu xenografts was decreased as early as 4 h after tumor irradiation, despite nonspecific uptake remaining unaltered. Tumor growth was inhibited after antiangiogenic or radiation therapy.
  
  
  CONCLUSIONS
  Here, it is suggested that (111)In-RGD2 could allow in vivo monitoring of angiogenic responses after radiotherapy and may therefore prove a good clinical tool to monitor angiogenic responses early after the start of radiotherapy in patients with head and neck squamous cell carcinoma. Despite clear antitumor efficacy, antiangiogenic therapy did not alter tumor uptake of (111)In-RGD2, indicating that integrin expression was not altered.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Department of Imaging Sciences, Kings College London, London, United Kingdom samantha.terry@kcl.ac.uk.
authors.forename: Samantha Y A
authors.initials: SY
authors.lastname: Terry
authors.affiliation: Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland; and.
authors.forename: Keelara
authors.initials: K
authors.lastname: Abiraj
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Lok
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Danny
authors.initials: D
authors.lastname: Gerrits
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006801:Humans; D007204:Indium / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009842:Oligopeptides / Q000737:chemistry*; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011868:Radioisotopes / Q000737:chemistry*; D000077157:Sorafenib; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009842:Oligopeptides; D010671:Phenylurea Compounds; D011868:Radioisotopes; D007204:Indium; D009536:Niacinamide; D000068258:Bevacizumab; C047981:arginyl-glycyl-aspartic acid; D000077157:Sorafenib
keywords: anti-angiogenic therapy; dimeric RGD; integrin αvβ3; monitor response; radiotherapy