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 Mottaghy*, Fabian Kiessling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)623-633
Number of pages11
JournalMolecular Imaging and Biology
Volume22
Issue number3
Early online date8 Aug 2019
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Duramycin
  • Apoptosis
  • Toxicity
  • PET
  • CT
  • Chemotherapy
  • PRECLINICAL EVALUATION
  • MOLECULAR-MECHANISMS
  • CISPLATIN
  • APOPTOSIS
  • THERAPY
  • MICE

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