title: A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe.
abstract: OBJECTIVE
  Molecular imaging of apoptosis is frequently discussed for monitoring cancer therapies. Here, we compare the low molecular weight phosphatidylserine-targeting ligand zinc2+-dipicolylamine (Zn2+-DPA) with the established but reasonably larger protein annexin V.
  
  
  METHODS
  Molecular apoptosis imaging with the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn2+-DPA (794 nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups were investigated: untreated controls and treated tumours after 1 or 4 days of anti-angiogenic therapy (SU11248). Additionally, μPET with 18 F-FDG was performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and validated by quantitative immunohistochemistry.
  
  
  RESULTS
  Compared with untreated control tumours, TUNEL staining indicated significant apoptosis after 1 day (P < 0.05) and 4 days (P < 0.01) of treatment. Concordantly, Zn2+-DPA uptake increased significantly after 1 day (P < 0.05) and 4 days (P < 0.01). Surprisingly, annexin V failed to detect significant differences between control and treated animals. Contrary to the increasing uptake of Zn2+-DPA, 18 F-FDG tumour uptake decreased significantly at days 1 (P < 0.05) and 4 (P < 0.01).
  
  
  CONCLUSIONS
  Increase in apoptosis during anti-angiogenic therapy was detected significantly better with the low molecular weight probe Zn2+-DPA than with the annexin V-based probe. Additionally, significant treatment effects were detectable as early using Zn2+-DPA as with measurements of the glucose metabolism using 18 F-FDG.
  
  
  CONCLUSIONS
  • The detection of apoptosis by non-invasive imaging is important in oncology. • A new low molecular weight probe Zn2+-DPA shows promise in depicting anti-angiogenic effects. • The small Zn2+-DPA ligand appears well suited for monitoring therapy. • Treatment effects are detectable just as early with Zn2+-DPA as with 18F-FDG.
authors.forename: Karin
authors.initials: K
authors.lastname: Palmowski
authors.forename: Anne
authors.initials: A
authors.lastname: Rix
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.forename: Florian F
authors.initials: FF
authors.lastname: Behrendt
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gray
authors.forename: Koon Y
authors.initials: KY
authors.lastname: Pak
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000588:Amines; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D017304:Annexin A5; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D015335:Molecular Probes; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D009942:Organometallic Compounds; D010848:Picolinic Acids; D011758:Pyrroles / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D000077210:Sunitinib; D014407:Tumor Cells, Cultured; D015032:Zinc
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D020533:Angiogenesis Inhibitors; D017304:Annexin A5; D007211:Indoles; D015335:Molecular Probes; D009942:Organometallic Compounds; D010848:Picolinic Acids; D011758:Pyrroles; C529174:bis-dipicolylamine-Zinc(II); D019788:Fluorodeoxyglucose F18; D015032:Zinc; D000077210:Sunitinib