Early Detection of Cardiotoxicity Using [64Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure

Cecilie Hoeeg, Bjarke Follin, Constance Eline Grandjean, Rasmus Sejersten Ripa, Annette Ekblond, Jens Kastrup, Tina Binderup, Andreas Kjaer*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [64Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography-computed tomography ([64Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure. Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg of DOX or left untreated. Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week 8. [64Cu]Cu-RGD PET/CT scans were performed in week 4. DOX treatment led to a decline in pump function as well as an increase in cardiac and thymic uptake of [64Cu]Cu-RGD. In addition, DOX altered cardiac gene expression, led to infiltration of immune cells, reduced endothelial content, and increased interstitial fibrosis. Furthermore, concentrations of inflammatory plasma proteins were increased in the DOX group. In conclusion, DOX treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted a low left ventricular ejection fraction in week 8.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume21
Issue number8
Number of pages12
ISSN1543-8384
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Keywords

  • cardiotoxicity
  • cobber-64
  • heart failure
  • inflammation
  • PET imaging

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