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. 2020 Jun;22(3):623-633.
doi: 10.1007/s11307-019-01417-3.

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

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  5   6 , Fabian Kiessling  7
Affiliations

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

Anne Rix et al. Mol Imaging Biol. 2020 Jun.

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.

Keywords: Apoptosis; Chemotherapy; Duramycin; PET/CT; Toxicity.

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