title: A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing.
abstract: The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We showed that the progression of prostate cancer could be monitored in vivo judging by the decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determined the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation.
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: Subrata K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Pilhan
authors.initials: P
authors.lastname: Kim
authors.forename: Xiao-an
authors.initials: XA
authors.lastname: Zhang
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Yun
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: Zdravka
authors.initials: Z
authors.lastname: Medarova
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D055088:Early Detection of Cancer / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D015032:Zinc / Q000032:analysis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002614:Chelating Agents; D005456:Fluorescent Dyes; D011725:Pyridines; C431843:tris(2-pyridylmethyl)amine; D015032:Zinc