A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques

Abstract

Gadolinium(III) ion (Gd(3+)) complexes are widely used as contrast agents in magnetic resonance imaging (MRI), and many attempts have been made to couple them to sensor moieties in order to visualize biological phenomena of interest inside the body. However, the low sensitivity of MRI has made it difficult to develop practical MRI contrast agents for in vivo imaging. We hypothesized that practical MRI contrast agents could be designed by targeting a specific biological environment, rather than a specific protein such as a receptor. To test this idea, we designed and synthesized a Gd(3+)-based MRI contrast agent, 2BDP3Gd, for visualizing atherosclerotic plaques by linking the Gd(3+)-complex to the lipophilic fluorophore BODIPY to stain lipid-rich environments. We found that 2BDP3Gd was selectively accumulated into lipid droplets of adipocytes at the cellular level. Atherosclerotic plaques in the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits were clearly visualized in T1-weighted MR images after intravenous injection of 2BDP3Gd in vivo.

Gadolinium(III)-DOTA Complex Functionalized with BODIPY as a Potential Bimodal Contrast Agent for MRI and Optical Imaging

“…The BODIPY dyes have been used in a variety of applications such as biological labels and probes [36][37][38], fluorescent probes [39], laser dyes [40,41], light emitting diodes [42], solar cells [43,44], and potential sensitizers in photodynamic therapy [45,46]. Although BODIPYs are versatile compounds with good optical properties, their use in developing bimodal contrast agents remain scarce [47][48][49][50][51][52]. 18 F labeled BODIPY derivatives have been recently suggested as bifunctional reporters for hybrid optical/positron emission tomography imaging [53,54].…”

Radiotracer in Kombination mit Magnetresonanz-Kontrastmittel für die simultane MR-PET-Bildgebung

“…Magnetresonanzbilder werden aus NMR-Signalen gewonnen, die hauptsächlich von Protonen aus Wassermolekülen stammen, sodass die Signalintensität weitgehend von der Konzentration und den Relaxationszeiten (T 1 und T 2 ) der Protonen in Wassermolekülen abhängt [4]. Kontrastmittel für die MR-Bildgebung, die auf paramagnetischen Metallen wie Gadolinium, Mangan oder Eisen basieren [5], wirken effektiv, indem sie die T 1 (Spin-Gitter)-Relaxationszeit von Wasserprotonen durch Förderung des schnellen Austauschs von Wassermolekülen in der Innenkugel mit Wasser in der Masse fördern und die Erhöhung der Signalintensität in T 1 -gewichteten MR-Bildern verkürzen [6]. Um Kontrast zu erhalten, sind jedoch große Mengen paramagnetischer Ionen im millimolaren Bereich erforderlich.…”

Pharmacokinetic modeling of Gadolinium nanoparticles (Gd-NPs) with the sojourn time in vasa vasorum for the contrast enhanced MRI

“…Usually, the contrast agents are presented in forms of nanoparticles (NPs) or liposomes containing metal ions such as iron(II), iron(III), gadolinium(II), gadolinium(III), manganese(II), or manganese(III) [10][11][12]. Gadolinium(III) complexes (gadolinium-based contrast agents (GBCAs) or gadolinium nanoparticles (Gd-NPs)) are the most widely clinically used agent through the intravenous route [13]. The working principle of Gd-NPs to assist the image acquisition is binding between the Gd-NPs and the specific biological environment such as molecular markers of disease.…”