Gadolinium-DOTA Enhanced MR Imaging of Intracranial Lesions

Parizel, Paul M.; Hr, Degryse; Gheuens, J.; Jj, Martin; M, Van Vyve; C, De La Porte; Selosse, P; Heyning, Paul Van de; Schepper, De

doi:10.1097/00004728-198905000-00002

Cited by 46 publications

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“…The simple tetraamide ligands DOTAM (1), its N-methyl analog DOTA-(MeAm) 4 (2), the Nethyl analog DOTA-(EtAm) 4 (3), and the glycinate ethyl ester analog DOTA-(gly-OEt) 4 (4) were prepared following established procedures by alkylation of 1,4,7,10-tetraazacyclododecane with the appropriate α-halo amide derivative. [12,[15][16][17][18] The characteristics of these ligands were in a good agreement with those reported previously.…”

Section: Resultsmentioning

confidence: 99%

“…The next two approved agents, [Gd(DTPA-BMA)] and [Gd(HP-DO3A)], derived from an open-chain DTPA ligand and a macrocyclic DOTA ligand, respectively, are both neutral complexes. [2][3][4] All four of these systems are nonadentate, with one Gd 3+ coordination site occupied by a water molecule. Rapid relaxation of this inner-sphere water molecule by the paramagnetic Gd 3+ results in a shortening of the bulk water proton relaxation time (T 1 ) through the rapid exchange of an inner-sphere bound water molecule with tissue water.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

et al. 2007

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Lanthanide complexes of tetraamide derivatives of DOTA are of interest today because of their application as chemical exchange saturation transfer (CEST) agents for magnetic resonance imaging (MRI). The protonation constants of some simple tetraamide derivatives of DOTA and the stability constants of the complexes formed with some endogenous metal ions, namely Mg 2+ , Ca 2+ , Cu 2+ , Zn 2+ , and lanthanide(III) ions, have been studied. These complexes were found to be considerably less stable than the corresponding [M(DOTA)] 2− complexes, largely due to the lower basicity of the tetraamide ligands. The Mg 2+ and Ca 2+ complexes are well described by formation of only ML species at equilibrium while the Zn 2+ and Cu 2+ complexes exhibit one and two additional deprotonation steps above a pH of around 6, respectively. The extra deprotonation that occurs at high pH for the [Zn{DOTA-(amide) 4 }] 2+ complexes has been assigned to an amide deprotonation by 1 H NMR spectroscopy. The first deprotonation step for the Cu 2+ complexes was traced to formation of the ternary hydroxo complexes ML(OH) (by UV/Vis spectrophotometry) while the second step corresponds to deprotonation of an amide group to form ML(OH)H −1 -type complexes. The trends in the stability constants of the [Ln{DOTA-(amide) 4 }] 3+ complexes follow similar trends with respect to ion size as those reported previously for the corresponding [Ln(DOTA)] − complexes, but again, the stability constants are about 10-11 orders of magnitude lower. A kinetic analysis of complex formation has shown that complexes are directly formed between a Ln 3+ cation and fully deprotonated L without formation of a protonated intermediate. [Ln{DOTA-(MeAm) 4 }] 3+ complex formation occurs at a rate that is two to three orders of magnitude slower than those of the corresponding [Ln(DOTA)] − complexes, while the variation in complex formation rates with Ln 3+ ion size is opposite to that observed for the corresponding [Ln(DOTA)] − complexes. The Ce 3+ and Correspondence to: Gyula Tircsó; A. Dean Sherry. Supporting information for this article is available on the WWW under http://www.eurjic.org or from the author. Eu 3+ complexes of DOTA-(MeAm) 4 are kinetically inert with respect to acid-catalyzed dissociation, which suggests that these complexes may potentially be safe for use in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

et al. 2007

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“…Furthermore, AuNPs in a variety of instances, including encapsulation within dendrimers, have also been shown to possess heightened biocompatibility and stability [15, 20, 21]. With regard to MRI, Gadolinium (Gd) chelated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a long recognized contrast agent because of its unique soft tissue resolving capabilities [22, 23]. When DOTA-Gd was conjugated to dendrimers, the relaxivity and retention time of the contrast agent was increased [24].…”

Section: Introductionmentioning

confidence: 99%

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells

et al. 2016

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Although many breast and lung cancers overexpress human epidermal growth factor receptor-2 (HER-2), no methods currently exist for effective and early detection of HER-2-positive cancers. To address this issue, we designed and synthesized dendrimer-based novel nano-imaging agents that contain gold nanoparticles (AuNPs) and gadolinium (Gd), conjugated with the humanized anti-HER-2 antibody (Herceptin). Generation 5 (G5) polyamidoamine (PAMAM) dendrimers were selected as the backbone for the nano-imaging agents due to their unique size, high ratio of surface functional groups and bio-functionality. We modified G5 PAMAM dendrimer surface with PEG and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators to encapsulate AuNPs and complex Gd. These dendrimer entrapped AuNPs were further conjugated with Herceptin through copper-catalyzed azide- alkyne click reaction to construct the nano-imaging agent Au-G5-Gd-Herceptin. The targeted nano-imaging agent bound selectively to HER-2 overexpressing cell lines, with subsequent internalization into the cells. More importantly, non-targeted nano-imaging agent neither bound nor internalized into cells overexpressing HER-2. These results suggest that our approach could provide a platform to develop nano-diagnostic agents or nano-therapeutic agents for early detection and treatment of HER-2-positive cancers.

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“…[1–3] A study has been done using Gd(DOTA) −1 as a contrast agent to study central nervous system, such as intracranial lesions. [4] While the brain images in rat obtained using Gd(DOTA) −1 and Gd(DTPA) −2 as contrast agents showed no significant differences in enhancement, a faster rate of clearance of the former was observed. [5] However, current clinically used small molecule extracellular MRI contrast agents have relatively short blood half-lives and easily extravasate into muscle or are quickly excreted from the body due to their low molecular weight.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI

Nwe

Milenic

Bryant

et al. 2011

Journal of Inorganic Biochemistry

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We report in vivo and in vitro MRI properties of six gadolinium-dendrimer and gadolinium-albumin conjugates of derivatized acyclic diethylenetriamine-N,N’,N’,N’’, N’’-pentaacetic acid (1B4M) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (C-DOTA). The three albumin-based agents have comparable protein to chelate ratios (1:16–18) as well as molar relaxivity (8.8–10.4 mM−1s−1). The three dendrimer based agents have blood clearance half-lives ranging from 17 to 66 min while that of the three albumin-based agents are comparable to one another (40–47 min). The dynamic image obtained from use of the albumin conjugate based on the macrocycle (C-DOTA) showed a higher contrast compared to the remaining two albumin based agents. Our conclusion from all of the results is that the macrocyclic-based (DOTA) agents are more suitable than the acyclic-based (1B4M) agent for in vivo use based on their MRI properties combined with the kinetic inertness property associated with the more stable Gd(III) DOTA complex.

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Gadolinium-DOTA Enhanced MR Imaging of Intracranial Lesions

Cited by 46 publications

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Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells

Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI

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Gadolinium-DOTA Enhanced MR Imaging of Intracranial Lesions

Cited by 46 publications

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Synthesis and Characterization of DOTA‐(amide)4 Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Synthesis and Characterization of DOTA‐(amide)4 Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells

Preparation, characterization and in vivo assessment of Gd-albumin and Gd-dendrimer conjugates as intravascular contrast-enhancing agents for MRI

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Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes

Synthesis and Characterization of DOTA‐(amide)₄ Derivatives: Equilibrium and Kinetic Behavior of Their Lanthanide(III) Complexes