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

doi:10.1007/s11307-019-01417-3

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 journal › Article › Academic › peer-review

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
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	https://doi.org/10.1007/s11307-019-01417-3
Publication status	Published - Jun 2020

Keywords

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

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10.1007/s11307-019-01417-3

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@article{f453e57d908c4d79a31f74cdc5d9f4c1,

title = "Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin",

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 = "Duramycin, Apoptosis, Toxicity, PET, CT, Chemotherapy, PRECLINICAL EVALUATION, MOLECULAR-MECHANISMS, CISPLATIN, APOPTOSIS, THERAPY, MICE",

author = "Anne Rix and Drude, \{Natascha Ingrid\} and Anna Mrugalla and Ferhan Baskaya and Pak, \{Koon Yan\} and Brian Gray and Hans-J{\"u}rgen Kaiser and Tolba, \{Ren{\'e} Hany\} and Eva Fiegle and Wiltrud Lederle and Mottaghy, \{Felix Manuel\} and Fabian Kiessling",

note = "Funding Information: This study was supported by BMBF (German Federal Ministry of Education and Research) project LiSyM (Grant No. 031L0041) and by DFG (German Research Foundation) research group FOR2591 (Grant No. 321137804). Publisher Copyright: {\textcopyright} 2019, World Molecular Imaging Society.",

year = "2020",

month = jun,

doi = "10.1007/s11307-019-01417-3",

language = "English",

volume = "22",

pages = "623--633",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer",

number = "3",

}

TY - JOUR

T1 - Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin

AU - Rix, Anne

AU - Drude, Natascha Ingrid

AU - Mrugalla, Anna

AU - Baskaya, Ferhan

AU - Pak, Koon Yan

AU - Gray, Brian

AU - Kaiser, Hans-Jürgen

AU - Tolba, René Hany

AU - Fiegle, Eva

AU - Lederle, Wiltrud

AU - Mottaghy, Felix Manuel

AU - Kiessling, Fabian

N1 - Funding Information: This study was supported by BMBF (German Federal Ministry of Education and Research) project LiSyM (Grant No. 031L0041) and by DFG (German Research Foundation) research group FOR2591 (Grant No. 321137804). Publisher Copyright: © 2019, World Molecular Imaging Society.

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Duramycin

KW - Apoptosis

KW - Toxicity

KW - PET

KW - CT

KW - Chemotherapy

KW - PRECLINICAL EVALUATION

KW - MOLECULAR-MECHANISMS

KW - CISPLATIN

KW - APOPTOSIS

KW - THERAPY

KW - MICE

U2 - 10.1007/s11307-019-01417-3

DO - 10.1007/s11307-019-01417-3

M3 - Article

C2 - 31396770

SN - 1536-1632

VL - 22

SP - 623

EP - 633

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 3

ER -

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

Abstract

Keywords

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