Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin |
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Authors: | Rix Anne Drude Natascha Ingrid Mrugalla Anna Baskaya Ferhan Pak Koon Yan Gray Brian Kaiser Hans-Jürgen Tolba René Hany Fiegle Eva Lederle Wiltrud Mottaghy Felix Manuel Kiessling Fabian |
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Institution: | 1.Institute for Experimental Molecular Imaging -Center for Biohybrid Medical Systems –CBMS, Medical Faculty, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany ;2.Department for Nuclear Medicine -Uniklinik RWTH Aachen, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany ;3.Molecular Targeting Technologies, Inc., West Chester, PA, USA ;4.Institute for Laboratory Animal Science, Medical Faculty, RWTH Aachen University, Aachen, Germany ;5.Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands ; |
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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. ProceduresTracer 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. ResultsIn 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. Conclusion68Ga]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. |
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