A low molecular weight zinc-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe

K. Palmowski, A. Rix, W. Lederle, F.F. Behrendt, F.M. Mottaghy, B.D. Gray, K.Y. Pak, M. Palmowski, F. Kiessling

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: 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, muPET 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. KEY POINTS: * The detection of apoptosis by non-invasive imaging is important in oncology. * A new low molecular weight probe Zn 2+-DPA shows promise in depicting anti-angiogenic effects. * The small Zn 2+-DPA ligand appears well suited for monitoring therapy. * Treatment effects are detectable just as early with Zn 2+-DPA as with 18 F-FDG.
Original languageEnglish
Pages (from-to)363-370
JournalEuropean Radiology
Volume24
Issue number2
DOIs
Publication statusPublished - 1 Jan 2014

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