Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18F-Labeled Lipophilic Cations
© 2019 by the Society of Nuclear Medicine and Molecular Imaging..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
|---|---|
| Enthalten in: |
Journal of nuclear medicine : official publication, Society of Nuclear Medicine - 60(2019), 12 vom: 30. Dez., Seite 1750-1756 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
McCluskey, Stuart P [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 29.06.2020 Date Revised 17.03.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.2967/jnumed.119.226787 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM297651854 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM297651854 | ||
| 003 | DE-627 | ||
| 005 | 20231225092446.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2967/jnumed.119.226787 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0992.xml |
| 035 | |a (DE-627)NLM297651854 | ||
| 035 | |a (NLM)31147403 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a McCluskey, Stuart P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Imaging of Chemotherapy-Induced Acute Cardiotoxicity with 18F-Labeled Lipophilic Cations |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.06.2020 | ||
| 500 | |a Date Revised 17.03.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 by the Society of Nuclear Medicine and Molecular Imaging. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 18F radiochemistry | |
| 650 | 4 | |a PET | |
| 650 | 4 | |a cardiotoxicity | |
| 650 | 4 | |a doxorubicin | |
| 650 | 4 | |a phosphonium cations | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Fluorine Radioisotopes |2 NLM | |
| 650 | 7 | |a Organophosphorus Compounds |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Fluorine-18 |2 NLM | |
| 650 | 7 | |a GZ5I74KB8G |2 NLM | |
| 700 | 1 | |a Haslop, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Coello, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Gunn, Roger N |e verfasserin |4 aut | |
| 700 | 1 | |a Tate, Edward W |e verfasserin |4 aut | |
| 700 | 1 | |a Southworth, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Plisson, Christophe |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Wells, Lisa A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of nuclear medicine : official publication, Society of Nuclear Medicine |d 1960 |g 60(2019), 12 vom: 30. Dez., Seite 1750-1756 |w (DE-627)NLM000042072 |x 1535-5667 |7 nnns |
| 773 | 1 | 8 | |g volume:60 |g year:2019 |g number:12 |g day:30 |g month:12 |g pages:1750-1756 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2967/jnumed.119.226787 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 60 |j 2019 |e 12 |b 30 |c 12 |h 1750-1756 | ||