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Multimodal Interventional Molecular Imaging of Tumor Margins and Distant Metastases by Targeting α v β 3 Integrin
Author(s) -
Bunschoten Anton,
Buckle Tessa,
Visser Nils L.,
Kuil Joeri,
Yuan Hushan,
Josephson Lee,
Vahrmeijer Alexander L.,
van Leeuwen Fijs W. B.
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200034
Subject(s) - biodistribution , integrin , molecular imaging , ex vivo , fluorescence lifetime imaging microscopy , in vivo , medicine , angiogenesis , imaging agent , nuclear medicine , fluorescence , cancer research , pathology , biology , receptor , physics , microbiology and biotechnology , quantum mechanics
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.