Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes

Geraldes, Carlos F. G. C.; Sherry, A. Dean; Lázár, István; Miseta, Attila; Bogner, Péter; Berényi, E.; Sumegi, B.; Kiefer, Garry E.; McMillan, Kirk; Maton, Frédéric; Müller, Robert N.

doi:10.1002/mrm.1910300607

Cited by 56 publications

(43 citation statements)

References 24 publications

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“…The r 1 relaxivity is about eight times higher compared to Gd-DOTA ( Table 1). The molecular structure of P792, which is based on a Gd-DOTA skeleton, is responsible for an appropriate electronic relaxation time (30,31). Its increased molecular size results in a decrease of the rotational movement (10 -12).…”

Section: Discussionmentioning

confidence: 99%

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

Ruehm

Christina

Violas

et al. 2002

Magnetic Resonance in Med

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The purpose of this study was to assess a new Gd-based macromolecular intravascular contrast agent (P792, Vistarem®; Laboratoire Guerbet, Aulnay sous Bois, France) for MR angiography (MRA). P792 is a macrocyclic gadolinium compound based on a gadoterate meglumine structure substituted by hydrophilic arms. In vitro imaging of phantoms containing varying concentrations of P792 and gadoterate meglumine (Gd-DOTA) was performed. In rabbits (N ‫؍‬ 5), arterial concentrations for P792 and Gd-DOTA were determined, and in vivo 3D MRA was performed. For gadolinium concentrations ranging from 200 to 3000 mol/l, in vitro imaging showed higher SNR values for P792 compared to Gd-DOTA. Determination of arterial Gd concentration showed comparable bolus phase curves for P792 and Gd-DOTA. With P792, higher concentrations were obtained due to a restricted diffusion into the interstitial space. P792 allowed acquisition of high-quality MR angiograms. Image quality was rated as superior for P792 in the post-bolus phase images. In conclusion, P792 appears to be well suited for highquality first-pass and equilibrium-phase MRA. The intravascular properties lead to an excellent signal in the vasculature, with limited background enhancement. Since the agent is rapidly renally excreted, it should be well suited for perfusion and permeability imaging. Contrast-enhanced MR angiography (MRA) has evolved into an accurate technique for the assessment of most vascular territories (1-7). The technique is based on the availability of high-performance gradient systems, and is capable of reducing data acquisition times sufficiently to collect an entire 3D data set during the arterial phase of intravenously administered extracellular contrast agents (8). The T 1 -shortening effect of gadolinium chelates allows select enhancement of the arterial lumen without depending on time-of-flight effects. This assures maximal contrast between the arterial lumen and surrounding tissues, and renders the technique less susceptible to flow-dependent artifacts.The extracellular nature of the paramagnetic gadolinium chelates leads to rapid diffusion into the extracellular fluid compartment, resulting in decreasing arterial signal intensity and concomitant enhancement within surrounding tissues. The short intravascular halflife requires optimal timing of the contrast bolus, and provides only a very limited time window for data collection during the arterial phase of the intravenously administered contrast bolus. Timing errors may render the examination suboptimal or nondiagnostic. Thus high contrast doses and fast injection rates are required to induce adequate T 1

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Section: Discussionmentioning

confidence: 99%

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

Ruehm

Christina

Violas

et al. 2002

Magnetic Resonance in Med

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“…[3,14,15,19,23] However, only limited data are available for Ln III complexes of the dota-like ligands with other numbers (two or three) of phosphorus-containing pendant arms. [24][25][26][27][28] The biological behaviour of lanthanideA C H T U N G T R E N N U N G (III) dota and dotp complexes is also different. The dota complexes have no significant preference for any organ, but the dotp complexes and other poly(phosphonic acid) ligands exhibit a high affinity for calcified tissues.…”

Section: A C H T U N G T R E N N U N G (Dotp)]mentioning

confidence: 98%

“…The dota complexes have no significant preference for any organ, but the dotp complexes and other poly(phosphonic acid) ligands exhibit a high affinity for calcified tissues. [29,30] However, the bone affinity is specific to the complexes of polyphosphonic acids, as complexes of other phosphorus-containing ligands, such as phosphinic acids [26] or phosphonic monoesters, [28,31] have no bone localisation. The complexes of monophosphorus acid dota derivatives again show biodistributions similar to those of dota complexes.…”

Section: A C H T U N G T R E N N U N G (Dotp)]mentioning

confidence: 99%

Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H₆do2a2p) in Solution and in the Solid State: Structural Studies Along the Series

Campello¹,

Lacerda²,

Pereira

et al. 2010

Chemistry A European J

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Complexes of 4,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (trans-H(6)do2a2p, H(6)L) with transition metal and lanthanide(III) ions were investigated. The stability constant values of the divalent and trivalent metal-ion complexes are between the corresponding values of H(4)dota and H(8)dotp complexes, as a consequence of the ligand basicity. The solid-state structures of the ligand and of nine lanthanide(III) complexes were determined by X-ray diffraction. All the complexes are present as twisted-square-antiprismatic isomers and their structures can be divided into two series. The first one involves nona-coordinated complexes of the large lanthanide(III) ions (Ce, Nd, Sm) with a coordinated water molecule. In the series of Sm, Eu, Tb, Dy, Er, Yb, the complexes are octa-coordinated only by the ligand donor atoms and their coordination cages are more irregular. The formation kinetics and the acid-assisted dissociation of several Ln(III)-H(6)L complexes were investigated at different temperatures and compared with analogous data for complexes of other dota-like ligands. The [Ce(L)(H(2)O)](3-) complex is the most kinetically inert among complexes of the investigated lanthanide(III) ions (Ce, Eu, Gd, Yb). Among mixed phosphonate-acetate dota analogues, kinetic inertness of the cerium(III) complexes is increased with a higher number of phosphonate arms in the ligand, whereas the opposite is true for europium(III) complexes. According to the (1)H NMR spectroscopic pseudo-contact shifts for the Ce-Eu and Tb-Yb series, the solution structures of the complexes reflect the structures of the [Ce(HL)(H(2)O)](2-) and [Yb(HL)](2-) anions, respectively, found in the solid state. However, these solution NMR spectroscopic studies showed that there is no unambiguous relation between (31)P/(1)H lanthanide-induced shift (LIS) values and coordination of water in the complexes; the values rather express a relative position of the central ions between the N(4) and O(4) planes.

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“…Despite the same number of gadolinium ions per molecule the greater relaxivity of P846 (32 s À1 mM À1 at 1.5 T, in a saline solution) compared with Gd-DOTA (3.5 s À1 mM À1 at 1.5 T, in a saline solution) can be explained by in part to the choice of the Gd skeleton, which gives P846 an appropriate electronic relaxation time (9,16,17) and by the greater molecular weight of A. JACQUIER ET AL.…”

Section: Myocardial and Blood Longitudinal Relaxation Timesmentioning

confidence: 96%

MR imaging assessment of the kinetics of P846, a new gadolinium‐based MR contrast medium, in ischemically injured myocardium

Jacquier

Wendland

et al. 2008

Contrast Media & Molecular

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The objectives of the study were: (1) to compare the kinetics of a new gadolinium-based low-diffusibility magnetic resonance (MR) contrast medium, P846 and Gd-DOTA in left ventricular (LV) blood and in normal and ischemically injured myocardium using inversion recovery echo-planar imaging (IR-EPI) and (2) to compare the enhancement pattern after injection of P846 with Gd-DOTA, using T1-weighted spin-echo imaging (T1-SE). Sixteen rats were subjected to left descending artery (LAD) occlusion for 30 min, followed by 2.5 h reperfusion. MR imaging was performed before and after administration of the contrast medium in two different groups of animals: one group (n = 8) received 0.05 mmol kg(-1) P846 and the other (n = 8) 0.1 mmol kg(-1) Gd-DOTA. A blipped IR-EPI and a multislice T1-SE were performed before injection and for 90 min after injection. T1-values were derived by fitting regional signal intensity on the IR-EPI images, the R1, DeltaR1 (R(1postcontrast) - R(1precontrast)) and DeltaR1 ratios were calculated in LV blood, normal and injured myocardium. On SE-T(1), the signal intensity ratio (SI) and extent of injury were measured. True infarct size was measured using histochemical staining. Changes in DeltaR(1) were 4.8 times greater with 0.05 mmol kg(-1) P846 than with 0.1 mmol kg(-1) Gd-DOTA in LV blood (6.3 +/- 0.9 vs 0.9 +/- 0.1 s(-1), p < 0.0001), normal (1.7 +/- 0.2 vs 0.34 +/- 0.03 s(-1), p < 0.0001) and ischemically injured myocardium (5.4 +/- 0.4 vs 1.6 +/- 0.1 s(-1), p < 0.0001). MR imaging experiments showed that the signal enhancement with P846 is longer (90 min), which might be explained by a lower diffusion of P846 compared with Gd-DOTA (30 min). P846 differentiates viable and nonviable myocardium. Despite lower gadolinium dose, P846 permits differentiation of viable and nonviable myocardium owing to a high contrast and a long imaging window with conventional t1-weighted SE sequence.

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Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes

Cited by 56 publications

References 24 publications

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H₆do2a2p) in Solution and in the Solid State: Structural Studies Along the Series

MR imaging assessment of the kinetics of P846, a new gadolinium‐based MR contrast medium, in ischemically injured myocardium

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Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes

Cited by 56 publications

References 24 publications

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

MR angiography with a new rapid‐clearance blood pool agent: Initial experience in rabbits

Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H6do2a2p) in Solution and in the Solid State: Structural Studies Along the Series

MR imaging assessment of the kinetics of P846, a new gadolinium‐based MR contrast medium, in ischemically injured myocardium

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Lanthanide(III) Complexes of 4,10‐Bis(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid (trans‐H₆do2a2p) in Solution and in the Solid State: Structural Studies Along the Series