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Targeted nanoparticles for multimodal imaging of the receptor for advanced glycation end-products
摘要： The receptor for advanced glycation end-products (RAGE) is implicated in multiple disease states such as cancer, diabetes and neurodegenerative disorders, and RAGE inhibitors are being explored as potential new therapies in such cases. Despite the known role RAGE plays in these conditions, there remains an urgent need for a molecular imaging agent that can accurately quantify RAGE levels in vivo, aid in validation of RAGE as a biomarker and/or therapeutic target, and support development of new RAGE inhibitors. This editorial highlights a multimodal nanoparticle-based imaging agent targeted at RAGE that was recently developed by Konopka and colleagues (Theranostics 2018; 8(18):5012-5024. doi:10.7150/thno.24791).
关键词： receptor for advanced glycation end-products,positron emission tomography,multimodal imaging
更新于2025-09-23 15:22:29
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Multimodal imaging of the receptor for advanced glycation end-products with molecularly targeted nanoparticles
摘要： The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE’s importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo. Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA). Methods: A multimodal tracer (64Cu-Rho-G4-CML) was developed using a generation-4 (G4) polyamidoamine (PAMAM) dendrimer, conjugated with both rhodamine and copper-64 (64Cu) chelator (NOTA) for optical and PET imaging, respectively. First, 64Cu-Rho-G4-CML and its non-targeted analogue (64Cu-Rho-G4-HSA) were evaluated chemically using techniques such as dynamic light scattering (DLS), electron microscopy and nuclear magnetic resonance (NMR). The tracers’ binding capabilities were examined at the cellular level and optimized using live and fixed HUVEC cells grown in 5.5-30 mM glucose, followed by in vivo PET-CT imaging, where the probes’ kinetics, biodistribution, and RAGE targeting properties were examined in a murine model of hindlimb ischemia. Finally, histological assessment of RAGE levels in both ischemic and non-ischemic tissues was performed. Conclusions: Our RAGE-targeted probe demonstrated an average size of 450 nm, a Kd of 340-390 nM, rapid blood clearance, and a 3.4 times greater PET uptake in ischemic RAGE-expressing hindlimbs than their non-ischemic counterpart. We successfully demonstrated increased RAGE expression in a murine model of hindlimb ischemia and the feasibility for non-invasive examination of cellular, tissue, and whole-body RAGE levels with a molecularly targeted tracer.
关键词： multimodal imaging,inflammation,receptor for advanced glycation end-products,hindlimb ischemia,PET-CT
更新于2025-09-23 15:21:01