Anne Rix1, Natascha Ingrid Drude1,2, Anna Mrugalla1, Ferhan Baskaya1, Koon Yan Pak3, Brian Gray3, Hans-Jürgen Kaiser2, René Hany Tolba4, Eva Fiegle1, Wiltrud Lederle1, Felix Manuel Mottaghy5,6, Fabian Kiessling7. 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 for Nuclear Medicine -Uniklinik RWTH Aachen, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. fmottaghy@ukaachen.de. 6. Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands. fmottaghy@ukaachen.de. 7. Institute for Experimental Molecular Imaging -Center for Biohybrid Medical Systems -CBMS, Medical Faculty, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany. fkiessling@ukaachen.de.
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.
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.
Authors: Mayara L C Dourado; Luca T Dompieri; Glauber M Leitão; Felipe A Mourato; Renata G G Santos; Paulo J Almeida Filho; Brivaldo Markman Filho; Marcelo D T Melo; Simone C S Brandão Journal: Arq Bras Cardiol Date: 2022-05-02 Impact factor: 2.667
Authors: Christophe Van de Wiele; Sezgin Ustmert; Bart De Spiegeleer; Pieter-Jan De Jonghe; Mike Sathekge; Maes Alex Journal: Int J Mol Sci Date: 2021-03-09 Impact factor: 5.923