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Journal ArticleDOI

153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

25 Jul 2002-Journal of Inorganic Biochemistry (Elsevier)-Vol. 91, Iss: 1, pp 312-319
TL;DR: Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp and the ligand DTPA(BOM) 3, were studied as potential hepatospecific gamma scintigraphic agents, showing that the main excretory pathway for all the chelates studied is the hepatobiliary system.
About: This article is published in Journal of Inorganic Biochemistry.The article was published on 2002-07-25 and is currently open access. It has received 10 citations till now.

Summary (1 min read)

Jump to:  and [1 . Introduction]

1 . Introduction

  • The Gd(III) complexes of both ligands, which have The primary objective of their work was to perform already been characterised [4] [5] [6] , show a high binding 31 biodistribution studies and obtain information about affinity to HSA, in particular Gd -L [6] .
  • Experimental carrier-mediated pathway, in common with taurocholate but not conjugated bilirubin [9], operated by the human 2 .1.
  • Reagents and apparatus liver organic anion transporting polypeptide (OATP) [12] .

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Citations
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Journal ArticleDOI
TL;DR: These studies have confirmed that the approximately four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions.
Abstract: {Fe[Gd2bpy(DTTA)2(H2O)4]3}4- is a self-assembled, metallostar-structured potential MRI contrast agent, with six efficiently relaxing Gd3+ centers confined into a small mol. space. Its proton relaxivity is particularly remarkable at very high magnetic fields (r1 = 15.8 mM-1 s-1 at 200 MHz, 37°C, in H2O). Here we report the first in vivo MRI feasibility study, complemented with dynamic g scintigraphic imaging and biodistribution expts. using the 153Sm-enriched compd. Comparative MRI studies have been performed at 4.7 T in mice with the metallostar and the small mol. wt. contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate ([Gd(DOTA)(H2O)]- = GdDOTA). The metallostar was well tolerated by the animals at the concns. of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg-1 body wt.; (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-1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T1), as calcd. 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 approx. 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 mol. wt., the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compd. having 153Sm enrichment also proved the renal elimination pathway. The biodistribution expts. 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.

72 citations


Cites methods from "153Sm3+ and 111In3+ DTPA derivative..."

  • ...To complement the MRI data, biodistribution and dynamic g scintigraphic studies were performed in Wistar rats using a metallostar solution where the gadolinium was replaced by a mixture of radioactive and non-radioactive samarium (13,14)....

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Journal ArticleDOI
TL;DR: In vitro experiments demonstrated that GdDOTP5−-induced changes in relaxivity were silenced upon HA binding but could be recovered by acid elution of the complex, suggesting a novel strategy for creating highly sensitive, switchable MRI contrast agents.
Abstract: Rationale and Objectives:GdDOTP5− is a highly charged, bone-seeking paramagnetic complex that could potentially detect bone lesions by magnetic resonance imaging (MRI). To date, its pharmacokinetics, effects on organ relaxivity, and interaction with hydroxyapatite (HA) has not been described.Methods

36 citations


Cites background from "153Sm3+ and 111In3+ DTPA derivative..."

  • ...tural differences between the 2 chelates, likely related to a lower coordination number for In(3) compared with Sm(3) .(6,36) In particular, (153)SmDOTP(5) is still significantly localized on bone 48 hours postinjection....

    [...]

Journal ArticleDOI
TL;DR: The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are indicative of a fast elimination via the kidneys, and the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions.
Abstract: Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.0 mM(-1) s(-1) for GdDOTA at 9.4 T, 37 degrees C, in H(2)O). Here we report an in vivo MRI feasibility study, complemented with dynamic gamma scintigraphic imaging and biodistribution experiments using the (153)Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd(3)L and the commercial contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd(3)L was well tolerated by the animals at the dose of 8 micromol Gd kg(-1) body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd(3)L injection than after GdDOTA injection at an identical dose. The relaxation rates, DeltaR(1), were calculated from the IR TrueFISP data. During the excretory phase, the DeltaR(1) for various tissues was similar for Gd(3)L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 micromol Gd kg(-1) body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd(3)L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd(3)L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd(3)L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are also indicative of a fast elimination via the kidneys.

34 citations


Cites methods from "153Sm3+ and 111In3+ DTPA derivative..."

  • ...In order to gain further insight into the in vivo behaviour of the trinuclear Gd3L, we performed biodistribution and dynamic g scintigraphic studies in Wistar rats using the Sm3þ analog complex where the gadolinium was replaced by a mixture of radioactive ((153)Sm) and non-radioactive samarium (22,23)....

    [...]

Journal ArticleDOI
TL;DR: This review discusses radiotheranostics with radiolanthanides, focusing on the design, development strategies, and medical applications of radiolAnthanide-labeled probes.

27 citations

Journal ArticleDOI
TL;DR: The bis-hydroxymethyl-substituted DTTA skeleton can be seen as a new lead for the synthesis of high relaxivity contrast agents, although its low thermodynamic and kinetic stability will limit its use to in vitro and animal studies.
Abstract: A novel bis-hydroxymethyl-substituted DTTA chelatorN′-Bz-C4,4′-(CH2OH)2-DTTA (1) and its DTPA analogue C4,4′-(CH2OH)2-DTPA (2) were synthesized and characterized. A variable-temperature 1H NMR spectroscopy study of the solution dynamics of their diamagnetic (La) and paramagnetic (Sm, Eu) Ln3+ complexes showed them to be rigid when compared with analogous Ln3+-DTTA and Ln3+-DTPA complexes, as a result of their C4,4′-(CH2OH)2 ligand backbone substitution. The parameters that govern the water1H relaxivity of the [Gd(1)(H2O)2]− and [Gd(2)(H2O)]2− complexes were obtained by 17O and 1H NMR relaxometry. While the relaxometric behaviour of the [Gd(2)(H2O)]2− complex is very similar to the parent [Gd(DTPA)(H2O)]2− system, the [Gd(1)(H2O)2]− complex displays higher relaxivity, due to the presence of two inner sphere water molecules and an accelerated, near optimal water exchange rate. The [Gd(1)(H2O)2]− complex interacts weakly with human serum albumin (HSA), and its fully bound relaxivity is limited by slow water exchange, as monitored by 1H NMR relaxometry. This complex interacts weakly with phosphate, but does not form ternary complexes with bidentate bicarbonate and L-lactate anions, indicating that the two inner-sphere water molecules of the [Gd(1)(H2O)2]− complex are not located in adjacent positions in the coordination sphere of the Gd3+ ion. The transmetallation reaction rate of [Gd(1)(H2O)2]− with Zn2+ in phosphate buffer solution (pH 7.0) was measured to be similar to that of the backbone unsubstituted [Gd(DTTA-Me)(H2O)2]−, but twice faster than for [Gd(DTPA-BMA)(H2O)]. The in vivo biodistribution studies of the 153Sm3+-labelled ligand (1) in Wistar rats reveal slow blood elimination and short term fixation in various organs, indicating some dissociation. The bis-hydroxymethyl-substituted DTTA skeleton can be seen as a new lead for the synthesis of high relaxivity contrast agents, although its low thermodynamic and kinetic stability will limit its use to in vitro and animal studies.

20 citations

References
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Book
01 Jan 1967
TL;DR: In this paper, a 2-volume work contains nuclear structure and decay data for over 3,100 isotopes and isomers and extensive appendices have been entirely rewritten, expediting retrieval and use of nuclear information for many areas of research.
Abstract: This 2-volume work contains nuclear structure and decay data for over 3,100 isotopes and isomers. Features: References data from thousands of pages of figures and tables. Encompasses about twice as much data as the previous edition. The extensive appendices have been entirely rewritten, expediting retrieval and use of nuclear information for many areas of research, and for users with varying levels of expertise.

4,018 citations

Book
19 Feb 2013
TL;DR: This paper presents physical principles of Medical Imaging by Nuclear Magnetic Resonance and EPR Methods in Contrast Agent Research: Examples from GdA+ Chelates, a comparison of Frequency and Frequency Aspects of Lanthanide(III) Complexes.
Abstract: Contributors. Preface. Physical Principles of Medical Imaging by Nuclear Magnetic Resonance (S. Mansson and A. Bjornerud). Relaxivity of Gadolinium (III) Complexes: Theory and Mechanism (E. Toth, et al.). Synthesis of MRI Contrast Agents I: Acyclic Ligands. (P. Anelli and L. Lattuada). Synthesis of MRI Contrast Agents II: Macrocyclic Ligands. (V. Jacques and J. Desreux). Protein--Bound Metal Chelates (S. Aime, et al.). Stability and Toxicity of Contrast Agents (E. Brucher and A. Sherry). Computational Studies Related to Gd(III)--Based Contrast Agents (D. Sulzle, et al.). Structure and Dynamics of Gadolinium--Based Contrast Agents (J. Peters, et al). Multi--Frequency and High--Frequency EPR Methods in Contrast Agent Research: Examples from GdA+ Chelates (R. Clarkson, et al). Particulate Magnetic Contrast Agents (R. Muller, et al). Photophysical Aspects of Lanthanide(III) Complexes (J. Bruce, et al).

996 citations

Journal ArticleDOI
TL;DR: As the first gadolinium-based blood pool agent in human trials, MS-325 has the potential to enhance both dynamic and steady-state MR angiograms and provides vascular signal enhancement superior to that provided with other agents.
Abstract: PURPOSE: To evaluate the protein-binding and signal enhancement characteristics of MS-325, a gadolinium-based magnetic resonance (MR) imaging blood pool agent that binds to albumin, and compare results with those obtained with existing gadolinium- and iron oxide-based agents. MATERIALS AND METHODS: Protein binding in human plasma was measured by means of ultrafiltration. T1 relaxation times (20 MHz) were measured in human plasma or ex vivo samples from rabbits and monkeys injected with 0.1 mmol of MS-325 per kilogram of body weight. Imaging (three-dimensional fast imaging with steady-state precession, or FISP) was performed at 1.0 T in phantoms, which contained varying concentrations of different agents, or rabbits after injection of 0.015-0.100 mmol/kg MS-325. RESULTS: MS-325 is 80%-96% bound in human plasma and exhibits a relaxivity approximately six to 10 times that of gadolinium diethylenetriaminepentaacetic acid (DTPA). Images of phantoms containing MS-325 were significantly brighter than those conta...

446 citations

Frequently Asked Questions (1)
Q1. What contributions have the authors mentioned in the paper "Sm and in dtpa derivatives with high hepatic specificity: in vivo and in vitro studies" ?

Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp ( L ) and the ligand DTPA ( BOM ) 1 3 153 31 111 31 ( BOM5benzyloxymethyl ) ( L ), radiolabelled with Sm and In, were studied as potential hepatospecific gamma scintigraphic 2 agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The La 31 1 and In chelates of L and L show some structural and dynamic differences in aqueous solution, as studied by H NMR spectroscopy.