title: Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
abstract: Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker.
  
  
  METHODS
  A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging.
  
  
  RESULTS
  Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry.
  
  
  CONCLUSIONS
  The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches.
authors: Department of Radiology, Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
authors: Tessa
authors: T
authors: Buckle
authors: Joeri
authors: J
authors: Kuil
authors: Nynke S
authors: NS
authors: van den Berg
authors: Anton
authors: A
authors: Bunschoten
authors: Hildo J
authors: HJ
authors: Lamb
authors: Hushan
authors: H
authors: Yuan
authors: Lee
authors: L
authors: Josephson
authors: Jos
authors: J
authors: Jonkers
authors: Alexander D
authors: AD
authors: Borowsky
authors: Fijs W B
authors: FW
authors: van Leeuwen
mesh_terms: D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D003952:Diagnostic Imaging / Q000379:methods*; D005240:Feasibility Studies; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: C514936:CXCR4 protein, mouse; D005456:Fluorescent Dyes; D010455:Peptides; D019718:Receptors, CXCR4