Abstract
Different classes of small- or nano-sized calcium-sensitive probes for magnetic resonance imaging (MRI) have been proposed in the last two decades. These compounds have been developed mainly for functional MRI purposes and tested in vivo in different animal models. Most of them are paramagnetic systems that change their relaxivity in the presence of the divalent ion calcium, resulting in increased T1 or T2 contrast. In this work, we report the investigation of their relaxometric behavior at low magnetic fields, specifically the comparison of the monomeric Ca-sensitive probe and the corresponding dendrimer conjugates of generations 0, 1 and 2 (G0, G1 and G2, respectively). As a result, a relaxivity hump between 10 and 100 MHz of the Larmor frequency progressively appeared with an increase in the size of the investigated contrast agent, indicative of a restricted rotational motion of the complexes as long as the size of the molecule increases. The same trend with a more pronounced effect was detectable in the presence of calcium. The relaxivity enhancement for the Ca2+ adducts, primarily caused by an increase of the hydration state of Gd3+, went from ca. 130% for the monomeric probe to ca. 310% for the G2 dendrimer conjugate at 0.5 T and 25 °C. T1 weighted magnetic resonance images acquired at 1 T displayed the strong ability of these systems to change their contrast according to the presence of calcium at this field, thus laying the basis for promising future in vivo applications.
Highlights
PaperJournal of Materials Chemistry B has been less studied, as its concentration remains constant during neuronal activity)
DCA0-2 samples were treated with ethylenediaminetetraacetic acid (EDTA) to remove the excess of Gd3+, while formed GdEDTA and remaining EDTA were removed from DCA0-2 by centrifugation using centrifugal filter units (3 kDa molecular weight cut-off)
We prepared a series of four smart contrast agents (SCAs) with different sizes, consisting of a typical monomacrocylic, DO3A-derived SCA and a triplet of dendrimeric conjugates of different generation (G0–2) bearing the same monomeric SCA unit
Summary
Journal of Materials Chemistry B has been less studied, as its concentration remains constant during neuronal activity). In particular, attracts considerable interest for functional MRI applications as it can aid tracking the neuronal activity in vivo. SCAs designed for calcium real-time MRI are generally composed of a calcium chelator linked to one or two MR reporting moieties. The first paramagnetic calcium sensitive compound developed was based on the common BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N0,N0-tetraacetic acid) calcium chelator attached to two units of the highly paramagnetic Gd3+ complex of 1,4,7,10 tetraazacyclododecane-1,4,7-tricarboxylic acid (Gd-DO3A).[28] Subsequently, SCAs composed of a modified EGTA chelator linked to two macrocyclic DO3A-derived moieties that bear a pair of Gd3+ ions were synthesized, resulting in excellent relaxivity performance.[29] A recent study with this smart probe demonstrated the capability to detect and monitor the time course of cerebral ischemia, announcing the exciting prospects of this class of functional biomarkers for future advancements in molecular imaging.[30]
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