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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with ¹⁸F-Labeled Lipophilic Cations.

ABSTRACT: Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an ¹⁸F-labeled lipophilic phosphonium cation, [1-(2-¹⁸F-fluoroethyl),1H[1,2,3]triazole-4-ethylene]triphenylphosphonium bromide (¹⁸F-MitoPhos), as a cardiac imaging agent, comparing it with leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin model. Methods: Cardiac uptake and response to decreased mitochondrial membrane potential of ¹⁸F-MitoPhos and ^99mTc-sestamibi were tested in isolated perfused rat hearts. Baseline pharmacokinetic profiles of ¹⁸F-MitoPhos and ¹⁸F-fluorobenzyltriphenylphosphonium and their response to acute doxorubicin-induced cardiotoxicity were assessed in rats in vivo (10, 15, or 20 mg of doxorubicin per kilogram, intravenously, 48 h beforehand). Results: Cardiac retention of ¹⁸F-MitoPhos was more than double that of ^99mTc-sestamibi in isolated perfused rat hearts. A favorable biodistribution of ¹⁸F-MitoPhos in vivo was observed, with heart-to-tissue ratios of 304 ± 186, 11.2 ± 1.2, and 3.8 ± 0.6 for plasma, liver, and lung, respectively (60 min). A significant dose-dependent loss of cardiac retention of ¹⁸F-MitoPhos was observed on doxorubicin treatment, with average cardiac SUV from 30 to 60 min (mean ± SD) decreasing from 3.5 ± 0.5 (control) to 1.8 ± 0.1 (doxorubicin, 20 mg/kg). Other assessed biomarkers showed no alterations. Conclusion: ¹⁸F-MitoPhos showed pharmacokinetic parameters suitable for cardiac imaging. A significant dose response of cardiac uptake to doxorubicin treatment was observed before detectable biomarker alterations. ¹⁸F-MitoPhos is therefore a promising tracer for imaging chemotherapy-induced cardiotoxicity. To our knowledge, this is the first demonstration of radiolabeled lipophilic cations being used for the PET imaging of chemotherapy-induced cardiotoxicity and indicates the potential application of these compounds in this area.

SUBMITTER: McCluskey SP

PROVIDER: S-EPMC6894381 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with <sup>18</sup>F-Labeled Lipophilic Cations.

McCluskey Stuart P SP Haslop Anna A Coello Christopher C Gunn Roger N RN Tate Edward W EW Southworth Richard R Plisson Christophe C Long Nicholas J NJ Wells Lisa A LA

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20190530 12

Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation PET tracers may be suitable for early detection of cardiotoxicity. This study aimed to evaluate an <sup>18</sup>F-labeled lipophilic phosphonium ...[more]

PMID: 31147403

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with ¹⁸F-Labeled Lipophilic Cations.

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with <sup>18</sup>F-Labeled Lipophilic Cations.

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18F-Labeled Lipophilic Cations.

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with <sup>18</sup>F-Labeled Lipophilic Cations.

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OmicsDI is part of the ELIXIR infrastructure

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Imaging of Chemotherapy-Induced Acute Cardiotoxicity with ¹⁸F-Labeled Lipophilic Cations.