Figure 2.

Molecular nuclear imaging elucidates anthracycline cardiotoxicity mechanisms. Anthracyclines can increase ROS levels (which can be assessed by nuclear tracer ¹⁸F-DHMT), which can activate MMPs (which can be assessed by ^99mTc-RP805) (bottom left), leading to adverse cardiac remodeling. ROS levels can also promote mitochondrial dysfunction, which can disrupt the mitochondrial membrane potential and thereby reduce ⁶⁸Ga-Galmydar uptake (middle bottom). Mitochondrial damage can lead to apoptosis, which can be detected by Annexin V positivity (detected by ^99mTc-Annexin (bottom right). Damage to cardiomyocytes can lead to release of intracellular myosin, which can thereby be assessed by (105). In-myosin (right of ROS). In addition to ROS increase, anthracyclines can also directly bind and inhibit Topoisomerase II, which can lead to double-stranded DNA breaks (right) and cause further mitochondrial dysfunction and prevent mitochondrial regeneration. Finally, anthracyclines can lead to impaired sympathetic innervation over time for mechanisms that are unclear but is associated with cardiac dysfunction and this can be assessed by ¹²³I-MIBG uptake (top left).