title: Noninvasive imaging of cell death using an Hsp90 ligand.
abstract: Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma membrane integrity. The compound is retained in the cytosol predominantly by covalent reaction with the 90 kDa heat shock protein (Hsp90), the most abundant molecular chaperone of the eukaryotic cytoplasm. The organoarsenical was tagged with either optical or radioisotope reporting groups to image cell death in cultured cells and in murine tumors ex vivo and in situ. Tumor cell death in mice was noninvasively imaged by SPECT/CT using an (111)In-tagged compound. This versatile compound should enable the imaging of cell death in most experimental settings.
authors.affiliation: Lowy Cancer Research Centre and POW Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Danielle
authors.initials: D
authors.lastname: Park
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Don
authors.forename: Tania
authors.initials: T
authors.lastname: Massamiri
authors.forename: Amol
authors.initials: A
authors.lastname: Karwa
authors.forename: Beth
authors.initials: B
authors.lastname: Warner
authors.forename: Jan
authors.initials: J
authors.lastname: MacDonald
authors.forename: Christine
authors.initials: C
authors.lastname: Hemenway
authors.forename: Arati
authors.initials: A
authors.lastname: Naik
authors.forename: Kah-Tiong
authors.initials: KT
authors.lastname: Kuan
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Dilda
authors.forename: Jason W H
authors.initials: JW
authors.lastname: Wong
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Lori
authors.initials: L
authors.lastname: Chinen
authors.forename: Mary
authors.initials: M
authors.lastname: Dyszlewski
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hogg
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000737:chemistry* / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000175:diagnosis; D016923:Cell Death; D015179:Colorectal Neoplasms / Q000175:diagnosis; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000175:diagnosis*; D004369:Pentetic Acid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011868:Radioisotopes / Q000737:chemistry
chemical_list: D001152:Arsenicals; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D018841:HSP90 Heat-Shock Proteins; D010455:Peptides; D011868:Radioisotopes; C046652:phenylarsonous acid; D004369:Pentetic Acid