Ferroptosis,
an iron-dependent regulated cell death, has been emerging
as an early mechanism in anticancer drug-induced acute kidney injury
(AKI) that may benefit therapeutic intervention. However, the lack
of molecular imaging methods for in vivo detection
of ferroptosis restricts the early diagnosis of anticancer drug-induced
AKI. Herein, we developed a PET/19F MRI dual-modal imaging
probe for the monitoring of ferroptosis in AKI by chemically conjugating
the Fe(II)-sensitive artemisinin (Art) motif and macrocyclic ligand
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to
the CF3-modified polyhedral oligomeric silsesquioxane (POSS)
clusters, denoted as the PAD probe. The PAD probe could be converted
into PA*D in the presence of Fe(II) ions and subsequently be intercepted
by biological macromolecules nearby, thereby enhancing the retention
effect in ferroptotic cells and tissues. After labeling with 68Ga isotopes, the 68Ga-labeled PAD probe in cisplatin
(CDDP)-induced AKI mice displayed a significantly higher renal uptake
level than that in normal mice. Moreover, the PAD probe with a precise
chemical structure, relatively high 19F content, and single 19F resonance frequency allowed for interference-free and high-performance19F MRI that could detect the onset of CDDP-induced AKI at
least 24 h earlier than the typical clinical/preclinical assays. Our
study provides a robust dual-modal molecular imaging tool for the
early diagnosis and mechanistic investigation of various ferroptosis-related
diseases.