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Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin

  • Anne Rix
  • Natascha Ingrid Drude
  • Anna Mrugalla
  • Ferhan Baskaya
  • Koon Yan Pak
  • Brian Gray
  • Hans-Jürgen Kaiser
  • René Hany Tolba
  • Eva Fiegle
  • Wiltrud Lederle
  • Felix Manuel MottaghyEmail author
  • Fabian KiesslingEmail author
Research Article

Abstract

Purpose

Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity.

Procedures

Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters.

Results

In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology.

Conclusion

[68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Key words

Duramycin Apoptosis Toxicity PET/CT Chemotherapy 

Notes

Funding

This study was supported by BMBF (German Federal Ministry of Education and Research) project LiSyM (Grant No. 031L0041) and by DFG (German Research Foundation) research group FOR2591 (Grant No. 321137804).

Compliance with Ethical Standards

All animal experiments were performed according to German legal requirements and animal protection laws, and were approved by the Authority for Environment Conservation and Consumer Protection of the State of North Rhine-Westphalia (LANUV).

Competing Interests

Brian D. Gray and Koon Y. Pak are employees, F. Kiessling is scientific advisor of Molecular Targeting Technologies, Inc. At all times, the other authors had full control over the study data and interpretation. No other potential conflicts of interest relevant to this article exist.

Supplementary material

11307_2019_1417_MOESM1_ESM.pdf (261 kb)
ESM 1 (PDF 260 kb)

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  • Anne Rix
    • 1
  • Natascha Ingrid Drude
    • 1
    • 2
  • Anna Mrugalla
    • 1
  • Ferhan Baskaya
    • 1
  • Koon Yan Pak
    • 3
  • Brian Gray
    • 3
  • Hans-Jürgen Kaiser
    • 2
  • René Hany Tolba
    • 4
  • Eva Fiegle
    • 1
  • Wiltrud Lederle
    • 1
  • Felix Manuel Mottaghy
    • 2
    • 5
    Email author
  • Fabian Kiessling
    • 1
    Email author
  1. 1.Institute for Experimental Molecular Imaging -Center for Biohybrid Medical Systems –CBMS, Medical FacultyRWTH Aachen UniversityAachenGermany
  2. 2.Department for Nuclear Medicine -Uniklinik RWTH Aachen, Medical FacultyRWTH Aachen UniversityAachenGermany
  3. 3.Molecular Targeting Technologies, Inc.West ChesterUSA
  4. 4.Institute for Laboratory Animal Science, Medical FacultyRWTH Aachen UniversityAachenGermany
  5. 5.Department of Radiology and Nuclear MedicineMaastricht University Medical Center (MUMC+)MaastrichtThe Netherlands

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