DOTAGA–Anhydride: A Valuable Building Block for the Preparation of DOTA‐Like Chelating Agents

Abstract

A DOTA derivative that contains an anhydride group was readily synthesized by reacting DOTAGA with acetic anhydride and its reactivity was investigated. Opening the anhydride with propylamine led to the selective formation of one of two possible regioisomers. The structure of the obtained isomer was unambiguously determined by 1D and 2D NMR experiments, including COSY, HMBC, and NOESY techniques. This bifunctional chelating agent offers a convenient and attractive approach for labeling biomolecules and, more generally, for the synthesis of a large range of DOTA derivatives. The scope of the reaction was extended to prepare DOTA-like compounds that contained various functional groups, such as isothiocyanate, thiol, ester, and amino acid moieties. This versatile building block was also used for the synthesis of a bimodal tag for SPECT or PET/optical imaging.

New 3‐(Heteroaryl)‐2‐iminocoumarin‐based Borate Complexes: Synthesis, Photophysical Properties, and Rational Functionalization for Biosensing/Biolabeling Applications

“…[27] One possible and often preferred way to access these multicomponent (bio)molecular systems is based on the synthesis and subsequent conjugation to ab iological vector of multimodal chelation (MMC) scaffolds, whichc ombine ab ifunctional chelating agentf or the selected metallic isotope and af luorescent organic dye into as ingle moiety. [28,29] The mostc ommon chelating agentsf or radiometals are cyclen derivatives (e.g., the "gold standard" chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) [30] )a nd someo ft hem are available in amine-reactive forms (e.g.,D OTA-NHS or DOTA-GA anhydride [31] ). In this context, we surmised that aminolysis of the NHS ester of DOTAb yf luorescent "7-hydroxy-Borico"-based benzylamine 9 would be an effective way to rapidly obtain af ully stable MMC scaffold (Scheme 5).…”

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].…”

“…An example of DOTA ligand functionalized with BODIPY compound was reported in 2010 by Bernhard et al [47] with the idea to generate a bimodal imaging agent for optical and nuclear imaging (PET/CT) by introducing In(III), Ga(III) and Cu(II) into the DOTA moiety. In 2012 the same group expanded their compound to a DOTAGA derivative (GA = glutaric acid) which gave more stable complexes with the transition metals [48,51,52]. Considering the versatility and favorable optical properties of BODIPY organic dyes, there are surprisingly very few examples of its use as an optical probe in the development of bimodal contrast agents.…”

Bifunctional Gallium-68 Chelators: Past, Present, and Future

“…[108][109][110] For a faster reaction with less side compounds DOTAGA-anhydride is superior to activated DOTAGA. 93 There are some examples for the use of DOTAGA and gallium. 94,111,112 The negative charge of 68 Ga-DOTAGA can be a problem for the affinity and the tumor to nontumor ratio.…”