Abstract
The importance of atherosclerosis is driving research to create improved diagnostic tools based on molecular imaging. Pretargeted imaging is the use of bioorthogonal probes that selectively accumulate upon reaction with a pre-modified biomolecule in vivo. To date, this very promising approach has not been applied to atherosclerosis. Neither has been the use of a single nano-radiomaterial for PET / T1-MR imaging of atherosclerosis. Here, we synthesized bioorthogonal nano-radiomaterials for in vivo pretargeted molecular imaging in a mouse model of atherosclerosis. Based on tetrazine-ligation, these functionalized 68Ga iron oxide nano-radiomaterials provide simultaneous PET and T1-MRI signals and selectively accumulate in atherosclerotic plaques in mice sequentially injected with trans-cyclooctene-modified antibodies against oxidized LDL followed by the hybrid nano-radiomaterial. Our results demonstrate the ability of this approach to unambiguously detect atherosclerosis. Furthermore, we show the first example of how hybrid imaging can be used for pretargeted bioorthogonal molecular imaging with nanomaterials.
Highlights
Atherosclerosis is a complex chronic inflammatory disease of the blood vessel wall in which plaques build up inside the arteries
Among the many targets present in the disease we focused in oxidized phospholipids, key compounds in the initiation and progression of atherosclerosis
The second component of the pretargeted imaging studied consisted on our 68Ga core-doped iron oxide nanoparticles, functionalized with TZ and, this way, ready for the biorthogonal reaction with the modified antibody
Summary
Atherosclerosis is a complex chronic inflammatory disease of the blood vessel wall in which plaques build up inside the arteries. We recently developed a new kind of nanoradiomaterial in which short half-life 68Ga isotopes are incorporated in the core of extremely small iron oxide particles, combining the size-dependent properties of nanotechnology with the unparalleled sensitivity of nuclear imaging techniques This nano-radiomaterial (NRM) provides simultaneous signals for PET and T1-MRI.. Bioorthogonal or pretargeted molecular imaging is based on the complementary labelling of the biomolecule (typically an antibody) and the probe; after injection of the biomolecule, the tracer is administered and selectively accumulates at the site of the bioorthogonal reaction This type of chemistry has many advantages in molecular imaging and is appealing since it allows the use of short half-life isotopes to detect biomolecules with long biodistribution times.. The extremely rapid reaction between trans-cyclooctene (TCO) and tetrazine (TZ) derivatives and the variety of compounds available make this reaction the first choice for many applications
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