title: Heptamethine cyanine based (64)Cu-PET probe PC-1001 for cancer imaging: synthesis and in vivo evaluation.
abstract: OBJECTIVE
  Development of a heptamethine cyanine based tumor-targeting PET imaging probe for noninvasive detection and diagnosis of breast cancer.
  
  
  METHODS
  Tumor-specific heptamethine-cyanine DOTA conjugate complexed with Cu-64 (PC-1001) was synthesized for breast cancer imaging. In vitro cellular uptake studies were performed in the breast cancer MCF-7 and noncancerous breast epithelial MCF-10A cell lines to establish tumor specificity. In vivo time-dependent fluorescence and PET imaging of breast tumor xenografts in mice were performed. Blood clearance, biodistribution, and tumor-specific uptake and plasma binding of PC-1001 were quantified. Tumor histology (H&E staining) and fluorescence imaging were examined.
  
  
  RESULTS
  PC-1001 displayed similar fluorescence properties (ε=82,880cm(-1)M(-1), Ex/Em=750/820nm) to the parental dye. Time-dependent cellular accumulation indicated significantly higher probe uptake (>2-fold, 30min) in MCF-7 than MCF-10A cells and the uptake was observed to be mediated by organic anion transport peptides (OATPs) system. In vivo studies revealed that PC-1001 has desirable accumulation profile in tumor tissues, with tumor versus muscle uptake of about 4.3 fold at 24h and 5.8 fold at 48h post probe injections. Blood half-life of PC-1001 was observed to be 4.3±0.2h. Microscopic fluorescence imaging of harvested tumor indicated that the uptake of PC-1001 was restricted to viable rather than necrotic tumor cells.
  
  
  CONCLUSIONS
  A highly efficient tumor-targeting PET/fluorescence imaging probe PC-1001 is synthesized and validated in vitro in MCF-7 breast cancer cells and in vivo in mice breast cancer xenograft model.
authors: Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA.
authors: Li
authors: L
authors: Xiao
authors: Yi
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Yue
authors: Xiuzhen
authors: X
authors: Xie
authors: Ji-Ping
authors: JP
authors: Wang
authors: Mahendra D
authors: MD
authors: Chordia
authors: Leland W K
authors: LW
authors: Chung
authors: Dongfeng
authors: D
authors: Pan
mesh_terms: D000818:Animals; D001692:Biological Transport; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002232:Carbocyanines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002471:Cell Transformation, Neoplastic; D060326:Chemistry Techniques, Synthetic; D003301:Copper Radioisotopes; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D049268:Positron-Emission Tomography; D013050:Spectrometry, Fluorescence; D047368:Tumor Burden
chemical_list: D002232:Carbocyanines; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
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