The Impact of Rigidity and Water Exchange on the Relaxivity of a Dendritic MRI Contrast Agent

Nicolle, Gaëlle M.; Tóth, Éva; Schmitt‐Willich, Heribert; Radüchel, Bernd; Merbach, André E.

doi:10.1002/1521-3765(20020301)8:5<1040::aid-chem1040>3.0.co;2-d

Cited by 162 publications

(161 citation statements)

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“…A Lipari-Szabo model of the inner sphere relaxivity was also used to take into account the rotational motion of the liposomal structure and that of the Gd-complex (Dunand et al 2001;Nicolle et al 2002). The rotational correlation time value of the liposome (s g ) calculated from the PCS diameter is of the order of 10 À4 s. This value was fixed during the fittings as well as s M that was fixed at 500 ns in order to reduce the number of fitted parameters.…”

Section: Resultsmentioning

confidence: 99%

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

et al. 2005

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Three amphiphilic DTPA bisamide derivatives containing long-chain phenylalanine esters (with 14, 16 and 18 carbon atoms in the alkyl chain) were synthesized and their corresponding gadolinium(III) complexes were prepared. The attempts to form paramagnetic micelles carrying the gadolinium(III) complexes yielded unstable or polydisperse micelles implying that the presence of the bulky aromatic side groups in the amphiphilic Gd-DTPA bisamide complexes results in an inefficient packing of the paramagnetic complex into micelles. All complexes were efficiently incorporated into liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), yielding stable and monodisperse paramagnetic liposomes. All liposomes had a comparable size, typically between 120 and 160 nm. As a result of the reduced mobility of the gadolinium(III) complexes, solutions of these supramolecular structures show a higher relaxivity than solutions of Gd-DTPA. However, the relaxivity gain is lower compared to compounds consisting of purely aliphatic chains of the same length, most likely due to the less efficient packing or increased local mobility of the gadolinium(III) complex. In the case of the Gd-DTPA bisamide complex with 18 carbon atoms, the immobilization inside the liposomal structure is less effective, probably because the aliphatic chains of the complex are longer than the alkyl chains of the DPPC host, resulting in a relatively high local mobility. The paramagnetic liposomes containing the Gd-DTPA bisamide complexes with 14 carbon atoms showed the highest relaxivity because the optimal length match between the hydrophobic chains of the DPPC and the ligand allowed very efficient packing of the paramagnetic complex into the liposome.

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Section: Resultsmentioning

confidence: 99%

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

et al. 2005

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“…[7] [Fe{Gd(tpy-DTTA)} 2 ] and [Fe{Gd(phen)(HDO3A)} 3 ] 2+ [4] are self-assembled structures. Gadomer 17, [10] [G5{Gd(DO3A)} 52 ], [11] and [G10{Gd(DOTA)} 1850 ] [8] are dendrimers. The effective relaxivities were calculated at 20 MHz and 37 8C, except for the last three columns which were determined at 25 8C.…”

Section: Angewandte Chemiementioning

confidence: 99%

High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

et al. 2005

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“…Several factors related to the linking strategy (such as the rigidity of the linkers, the interaction of Gd-complexing ligands with protein residues, and the flexibility of the protein region containing the amino acid being modified) may also affect the overall relaxivity values in complex ways. [21][22][23][24] Therefore, detailed studies of the relaxometric properties are needed to determine the influence of these factors.To do this, we report herein a detailed analysis of the NMRD profiles and physical parameters of two viral-capsid based contrast agents. Recently we have described the covalent attachment of HOPO based chelates to either the exterior or the interior surface of bacteriophage MS2 capsids devoid of nucleic acids.…”

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“…The parameters obtained for these Gd-HOPO virus conjugates can be compared to the parameters reported for Gd-DOTA (commercially available as DOTAREM) 42 dendrimer based conjugates, Gadomer 17 21 and PAMAM-G4-[Gd(DOTA-pBn)(H 2 O)] -33 43 (Table 2). These dendrimeric conjugates are obtained through the covalent attachment of multiple Gd-DOTA units to polyamine based dendrimers.…”

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High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

et al. 2008

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High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd 3+ ion) of 41.6 mM -1 s -1 at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal (τ Rl = 440 ps) and external (τ Rl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups. MANUSCRIPT TEXTMagnetic resonance imaging (MRI) is a routinely used noninvasive diagnostic technique, providing detailed images without the use of ionizing radiation. Although the resolution of MRI is excellent, its dynamic range is relatively narrow because of the limited variation in relaxation rates exhibited by water protons in vivo. When these differences are insufficient to distinguish between adjacent tissues, contrast enhancement is often achieved through the administration of synthetic agents that increase the water proton relaxation rates in accessible locations. Gadolinium complexes are the most often used for this purpose, with more than 10 million MRI studies being performed through their use each year. [2][3][4] The current commercially available Gd(III)-based contrast agents use poly(aminocarboxylate) chelates, and typically gram quantities of Gd must be injected to reach concentrations sufficient for usable contrast enhancement. However, this strategy is more difficult to apply to the specific imaging of biomarkers present in low (μM -nM) concentrations. To distinguish these sites from the background signal, targetable contrast agents will undoubtedly require significantly improved contrast enhancement efficiencies. 3,5 2 MRI contrast agents are commonly evaluated on the basis of relaxivity (r 1p ), which describes their ability to increase the longitudinal relaxation rate of nearby water molecule protons per millimolar concentration of agent applied. 6 Strategies for enhancing the relaxivity of contrast agents include increasing the number of bound water molecules (q), optimizing the water-residence time (τ M ) and increasing the rotational correlati...

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The Impact of Rigidity and Water Exchange on the Relaxivity of a Dendritic MRI Contrast Agent

Cited by 162 publications

References 36 publications

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

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The Impact of Rigidity and Water Exchange on the Relaxivity of a Dendritic MRI Contrast Agent

Cited by 162 publications

References 36 publications

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

Paramagnetic liposomes containing amphiphilic bisamide derivatives of Gd-DTPA with aromatic side chain groups as possible contrast agents for magnetic resonance imaging

High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents1

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High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹