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 language | English |
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Pages (from-to) | 623-633 |
Number of pages | 11 |
Journal | Molecular Imaging and Biology |
Volume | 22 |
Issue number | 3 |
Early online date | 8 Aug 2019 |
DOIs | |
Publication status | Published - Jun 2020 |
Keywords
- Duramycin
- Apoptosis
- Toxicity
- PET
- CT
- Chemotherapy
- PRECLINICAL EVALUATION
- MOLECULAR-MECHANISMS
- CISPLATIN
- APOPTOSIS
- THERAPY
- MICE