Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Abstract

À ¼ GdDOTA). The metallostar was well tolerated by the animals at the concentrations of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg À1 body weight; (BW). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the high-dose metallostar injection was considerably higher than after GdDOTA injection (0.1 mmol Gd kg À1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T 1 ), as calculated from the inversion recovery true fast imaging with steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA or the low dose metallostar injection. In summary, these studies have confirmed that the approximately four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions. The pharmacokinetics of the metallostar was found to be similar to that of GdDOTA, involving fast renal clearance, a leakage to the extracellular space in the muscle tissue and no leakage to the brain. As expected on the basis of its moderate molecular weight, the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compound having 153 Sm enrichment also proved the renal elimination pathway. The biodistribution experiments are in full accordance with the MR and scintigraphic imaging. At 15 min post-injection the activity is primarily localized in the urine, while at 24 h post-injection almost all radioactivity is cleared from tissues and organs.

In vivo MRI assessment of a novel GdIII‐based contrast agent designed for high magnetic field applications

“…The cortex and medulla showed a similar clearance pattern, with a slower rate for medulla. As the elimination rate depends on the dose administered (15), the elimination curves observed for GdDOTA are slightly different from those described in Livramento et al (8) as a consequence of the lower dose used here. For both CAs, the elimination curve approached a steady-state $3 min after injection (a slowly descending segment, corresponding to the predominant excretory function).…”

“…Recently we have reported a self-assembled metallostar system with remarkably high in vitro relaxivities at 200 and 400 MHz (6,7). The high efficacy of the metallostar has also been confirmed under in vivo conditions in mice in a comparative MRI study (8). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the injection of the metallostar at 0.05 mmol Gd kg À1 body weight (BW) was considerably higher than after GdDOTA injection (at 0.1 mmol Gd kg À1 BW), despite the higher dose of the latter.…”

Biocytin-Based Contrast Agents for Molecular Imaging: An Approach to Developing New In Vivo Neuroanatomical Tracers for MRI

“…This is in reference to the Solomon-Bloembergen-Morgan theory envisaging that at high magnetic fields, the longitudinal proton relaxivity changes with the opposite of molecular rotational correlation time (τ R ) suggesting that relaxivity change should be expected upon binding of the CAs to macromolecules (Livramento et al, 2006 …”

Smart MR Imaging Agents Relevant to Potential Neurologic Applications

“…The pharmacokinetics of this metallostar, injected intravenously, were found to be similar to that of Gd-DOTA, involving fast renal clearance and a leakage to the extracellular space in the muscle tissue. 41 Recently, another high-molecular-weight tetrametallic supramolecular complex [(Gd-DTPA-phenantroline) 3 Fe] has been obtained on self-assembly around 1 Fe 2ϩ ion. The slower elimination of the compound from rats as compared with Gd-DTPA was found to correlate with a reduced volume of distribution and suggests that the complex is confined to the blood compartment.…”