European Radiology

, Volume 24, Issue 2, pp 363–370 | Cite as

A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe

  • Karin Palmowski
  • Anne Rix
  • Wiltrud Lederle
  • Florian F. Behrendt
  • Felix M. Mottaghy
  • Brian D. Gray
  • Koon Y. Pak
  • Moritz Palmowski
  • Fabian Kiessling
Molecular Imaging

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, 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.

Key points

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 with18F-FDG.

Keywords

Apoptosis Molecular imaging Tumour Therapy monitoring Optical imaging Annexin V Zn2+-DPA 

Abbreviations

CT

computed tomography

F-FDG

18 F-fluorodeoxyglucose

MW

molecular weight

PET

positron emission tomography

PSVue794

brand name of fluorescently labelled Zn2+-DPA

ROI

region of interest

Zn2+-DPA

bis(zinc2+-dipicolylamine)

Notes

Acknowledgement

This work was supported by the HighTech.NRW/EU-Zeal 2-Program (EFRE); ForSaTum. The probe PSVue794 and the control probe to PSVue794 were kindly provided by Molecular Targeting Technologies, Inc. (West Chester, PA, USA). The authors Brian D. Gray and Koon Y. Pak are employees of Molecular Targeting Technologies, Inc. At all times, the other authors had full control over the study data and interpretation.

Moritz Palmowski and Fabian Kiessling contributed equally to this work.

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Copyright information

© European Society of Radiology 2013

Authors and Affiliations

  • Karin Palmowski
    • 1
    • 2
  • Anne Rix
    • 1
  • Wiltrud Lederle
    • 1
  • Florian F. Behrendt
    • 3
  • Felix M. Mottaghy
    • 3
    • 4
  • Brian D. Gray
    • 5
  • Koon Y. Pak
    • 6
  • Moritz Palmowski
    • 1
    • 3
    • 6
  • Fabian Kiessling
    • 1
  1. 1.Department of Experimental Molecular ImagingRWTH-Aachen UniversityAachenGermany
  2. 2.Department of Pneumology, Thoraxklinik HeidelbergUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of Nuclear MedicineRWTH-Aachen UniversityAachenGermany
  4. 4.Department of Nuclear MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
  5. 5.Molecular Targeting Technologies, Inc.West ChesterUSA
  6. 6.Academic Radiology Baden-Baden, Diagnostic and Interventional RadiologyUniversity Medical Center HeidelbergHeidelbergGermany

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