title: Multimodal interventional molecular imaging of tumor margins and distant metastases by targeting αvβ3 integrin.
abstract: α(v)β(3) integrin is involved in (tumor-induced) angiogenesis and is a promising candidate for the specific visualization of both primary tumors and of their distant metastases. Combination of radioactive and fluorescent imaging labels in a single multimodal, or rather hybrid, RGD-based imaging agent enables integration of pre-, intra-, and postoperative angiogenesis imaging. A hybrid imaging agent targeting the α(v)β(3) integrin--(111)In-MSAP-RGD (MSAP = multifunctional single-attachment-point reagent), which contains a targeting moiety, a pentetic acid (DTPA) chelate, and a cyanine dye--was evaluated for its potential value in combined lesion detection and interventional molecular imaging in a 4T1 mouse breast cancer model. SPECT/CT and fluorescence imaging were used to visualize the tumor in vivo. Tracer distribution was evaluated ex vivo down to the microscopic level. The properties of (111)In-MSAP-RGD were compared with those of (111)In-DTPA-RGD. Biodistribution studies revealed a prolonged retention and increased tumor accumulation of (111)In-MSAP-RGD relative to (111)In-DTPA-RGD. With (111)In-MSAP-RGD, identical features could be visualized preoperatively (SPECT/CT) and intraoperatively (fluorescence imaging). As well as the primary tumor, (111)In-MSAP-RGD also enabled detection and accurate excision of distant metastases in the head and neck region of the mice. Therefore, the hybrid RGD derivative (111)In-MSAP-RGD shows potential in preoperative planning and fluorescence-based surgical intervention.
authors.affiliation: Interventional Molecular Imaging, Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Bunschoten
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.forename: Nils L
authors.initials: NL
authors.lastname: Visser
authors.forename: Joeri
authors.initials: J
authors.lastname: Kuil
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
mesh_terms: D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D007205:Indium Radioisotopes / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000737:chemistry; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D009942:Organometallic Compounds; C047981:arginyl-glycyl-aspartic acid