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

Abstract

The synthesis and characterization of a novel gadolinium(III) DOTA complex functionalized with a boron-dipyrromethene derivative (BODIPY) is described. The assembly of the complex relies on azide diazotransfer chemistry in a copper tube flow reactor. The azide thus formed is coupled directly with an alkyne via click chemistry, resulting into a paramagnetic and luminescent gadolinium(III) complex. Luminescent data and relaxometric properties of the complex have been evaluated, suggesting the potential applicability of the complexes as a bimodal contrast agent for magnetic resonance and optical imaging. The complex displays a bright emission at 523 nm with an absorption maximum of 507 nm and high quantum yields of up to 83% in water. The proton relaxivity of the complex measured at 310 K and at frequencies of 20 and 60 MHz had the values of 3.9 and 3.6 s −1 •mM −1 , respectively.

A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry

“…Accordingly,C u II could be quickly and quantitatively removedf rom TRAP derivatives like 7 and 11 after CuAAC functionalization by the addition of excess NOTA and acidification to pH 2-3 or,e ven more conveniently,b y simply adding excessN OTA·3HCl. [48][49][50] Owing to the high thermodynamic stability and pronounced kinetic inertness of Ln III -DOTAc omplexes, [51] transmetalation with Cu II appearsn ot to be an issue here. Because scavengers like NOTAd on ot interfere with virtually any biogenic substrate, the transchelation approachr epresents av aluable alternative to sulfide-mediated demetalation.…”

Metal-based BODIPY derivatives as multimodal tools for life sciences

“…In a second step, ex vivo fluorescence microscopy studies enabled to visualize the accumulation of the tracer in the liver. In this study, [ 111 In]-4.1-1 proved to be a relevant tool to support the fact that pro-inflammatory LPS can be transported from the periphery to the liver for detoxification. In radiosignal can be detected in some mice at the injection site (jugular vein).…”

“…In another study, it was taken advantage of the isothiocyanate function of 4.1-1 to enable its bioconjugation to LPS (lipopolysaccharide) ( Figure 17) [105]. After radiolabeling with [ 111 In]-indium, [ 111 In]-20 was injected into wild-type C57B16 mice, and in vivo biodistribution of the resulting radioconjugate was performed by SPECT-CT imaging. In a second step, ex vivo fluorescence microscopy studies enabled to visualize the accumulation of the tracer in the liver.…”

ChemInform Abstract: A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry

“…[47] Notwithstanding this, CuAACc oupling of alkyne-functionalized [Gd III (DOTA)] units to various substrates, for example to the ubiquitous cyclo(RGDfK) peptide (Figure 9), has been performed without complications. [48][49][50] Owing to the high thermodynamic stability and pronounced kinetic inertness of Ln III -DOTAc omplexes, [51] transmetalation with Cu II appearsn ot to be an issue here. Hence, such Gd III chelates are ideal building blocksf or adding an MRI contrast agentf unctionality to any substrate by meanso fc lick chemistry,r endering CuAAC af irstrate reaction in this context.…”