The Use of the Macrocyclic Chelator DOTA in Radiochemical Separations

Abstract

Radiometals play an important role in the diagnosis of physiological processes in vivo by means of imaging technologies, but also increasingly contribute to the treatment of diseases. The by far dominant way to apply the advantages of nuclear transformations of radiometals is the use of radiometalligand complexes. In this context, it turns out that DOTA (and its derivatives) currently is the most potent chelator. This article reviews the physico-chemical properties of DOTA and its [*M(DOTA)]complexes, which made the DOTA moiety the dominant chelator for theranostics in radiopharmaceutical chemistry and nuclear medicine. Interestingly, and beyond nu- [a] Bracco Imaging spa, 38[a] Log K M(DOTA) ; 23.0 (Nd), [26] 23.5 (Eu), [26] 24.2 (Tb), [26] 25.0 (Yb); [26] log K ML values of M(DO3A) complexes: log K Y(DO3A) = 21.1; [31] log K La(DO3A) = 18.63; [8] log K Gd(DO3A) = 21.56; [8] log K Lu(DO3A) = 21.44; [8] log K Bi(DO3A) = 26.85. [32] Eur. J. Inorg. Chem. 2020, 36-56 www.eurjic.org

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“…Additionally, the high concentration of HCl not only converted 68 Ga-colloids into ionic [ 68 Ga]Ga 3+ travelling with the solvent front. Besides that, it seemed to facilitate the H + -assisted dissociation of the DOTA complex [ 47 , 48 , 49 ].…”

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“…9c and Table 5). 11,53 These examples show that 89 Y chemical shift is highly dependent on its coordination environment with large (B80 ppm) shift differences reported for hyperpolarised 89 Y nuclei coordinated to various different macrocyclic ligands. Such high sensitivity of 89 Y chemical shift to molecular environment has been exploited to design hyperpolarised 89 Y pH sensitive probes.…”

“…The stability of these metal ion complexes can be increased by synthesising analogues with greater backbone rigidity. 11 For example, CHX-A 00 -DTPA is a common derivative of DTPA that contains a rigid cyclohexane group in the DTPA backbone resulting in an increase in log K from 22.5 to 24.7 for Y-DTPA and Y-CHX-A 00 -DTPA respectively. 12 The geometry of the Y 3+ complex is also affected by CN and ligand denticity.…”

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“…NOTA has the smaller chelating cavity of the two, and is generally used for Ga (III) or Cu (II) because it has a particular attraction for these metals, which results in mild radiolabeling conditions and good in vivo stability of the complexes formed. DOTA (which is considered as the gold standard chelator) and its derivatives play an important role in clinical applications because they form very stable complexes with a wide range of trivalent radiometals such as Ga (III), Y (III), In (III), Lu (III), or even divalent such as Cu (II) [ 57 , 58 ]. For DOTA or NOTA, the introduction of a functionalized arm offers the possibility of coupling a biomolecule (NODASA/NODAGA and DOTASA/DOTAGA).…”