Magnetic resonance imaging contrast agents: Theory and the role of dendrimers

Wiener, Erik C.; Narayanan, Venkatraj V.

doi:10.1016/s1874-5229(02)80006-5

Cited by 14 publications

(26 citation statements)

References 297 publications

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“…Conjugating Gd 3 + complexes to dendrimers is a common strategy for slowing the rotational dynamics of paramagnetic complexes. [30][31][32][33][34][35][36][37] In order to quantitatively describe the rotational dynamics of these dendrimer systems, the Lipari-Szabo approach is typically used. [38][39][40][41][42][43] This model employs two correlation times; a long correlation time that defines the global motion of the entire dendrimer conjugate, t g , and a second shorter correlation time, t l , that reflects the local motion of the metal complex about its point of attachment to the dendrimer.…”

Section: Resultsmentioning

confidence: 99%

“…Current methods for assessing tissue pH involve relatively invasive procedures and typically can assess pH only from a limited number of locations. [2][3][4] Less invasive techniques such as 31 P NMR NMR spectroscopy [4] can provide a direct measure of pH but the concentrations of the endogenous phosphorus metabolites that respond to tissue pH are relatively low so pH measurements can only be taken from relatively large volumes of tissue. pH sensitive fluorescence dyes are quite sensitive but applications of optical techniques in human imaging is limited to tissues near the surface of skin where sufficient light penetration can be achieved.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Ali

Woods

Caravan

et al. 2008

Chemistry A European J

107

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The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the "on" state compared to that of the "off" state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing-Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8 mM(-1) s(-1) (pH 9) to 24.0 mM(-1) s(-1) (pH 6) per Gd(3+) ion. This more than doubles the relaxivity pH response, Deltar(1), of our agent from just 51 % for the original low molecular weight chelate to 122 % for the dendrimer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Ali

Woods

Caravan

et al. 2008

Chemistry A European J

107

View full text Add to dashboard Cite

show abstract

“…Therefore, dendrimers have highly branched, well‐defined, monodisperse architectures that, in many instances, originate from a multivalent core. As a result, these branched motifs are characterized by a large number of surface or terminal groups; their unique physical and chemical properties have been used in applications such as catalytic substrates,9–13 novel amphiphiles,14–16 complexing vehicles,17 and magnetic resonance imaging contrast agents 18, 19…”

Section: Introductionmentioning

confidence: 99%

Thermal behavior of metallodendrimers possessing bis(terpyridinyl)Ru^(II) connectivity and different surface functionality

Hwang

Yoo

Moorefield

et al. 2004

J Polym Sci B Polym Phys

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A series of metallodendrimers, assembled by means of bis(terpyridinyl)-Ru (II) connectivity on poly(propylene imine) dendrimer scaffolds, with homogeneous or heterogeneous surfaces, were prepared. Differential scanning calorimetry and thermogravimetric analysis were used to determine their thermal behavior, glass-transition temperatures, and the decomposition kinetics and temperatures; no synergy effects for these properties were observed for the heterogeneously surfaced constructs in contrast to the corresponding homogeneously coated materials, which exhibited different values depending on their surface functionalities.

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“…By appropriately selecting the various structural features of the backbone and by introducing specific terminal functionalities dendrimers can be tailored to serve as powerful tools in a wide variety of scientific areas, e.g., chemical catalysis [2], optics [3], electronics [4], environmental remediation [5], and life sciences. The promising applications of dendrimers in life sciences range from gene and drug delivery [6][7][8], therapy of malignancies [9] to in vitro and in vivo diagnostics [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive profiling of the complex dendrimeric contrast agent Gadomer using a combined approach of CE, MS, and CE‐MS

et al. 2007

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The complex dendrimeric contrast agent Gadomer has been comprehensively characterized using various mass spectrometric techniques in combination with capillary electrophoresis. The analytical challenges arising from the structure of this analyte, e.g., the presence of a complex isotopic pattern originating from multiple gadolinium chelates could be overcome using this combined approach. Results obtained from initial MALDI-TOF-MS measurements could subsequently be complemented and confirmed by CE-ESI-TOF-MS measurements. Furthermore, high resolution Fourier transform-ion cyclotron resonance-MS (FT-ICR-MS) as a stand alone technique and in combination with CE was performed to obtain mass spectra of high mass accuracy and resolution of various impurities and related dendrimers present in low concentrations in several Gadomer batches. The profile of related dendrimers and impurities of lower molecular weight present in Gadomer could be elucidated and variances in the pattern of related dendrimers present in batches obtained via different synthetic routes could be detected. The qualitative analysis of Gadomer using MS techniques in combination with CE provides the fundamental basis for a framework of analytical methodologies for the characterization of Gadomer. By designing such a framework of methodologies the challenges associated with the introduction of dendrimers into the clinical stage may be overcome and the reproducible quality and safety of these innovative products can be ensured.

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Magnetic resonance imaging contrast agents: Theory and the role of dendrimers

Cited by 14 publications

References 297 publications

Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Thermal behavior of metallodendrimers possessing bis(terpyridinyl)Ru^(II) connectivity and different surface functionality

Comprehensive profiling of the complex dendrimeric contrast agent Gadomer using a combined approach of CE, MS, and CE‐MS

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Magnetic resonance imaging contrast agents: Theory and the role of dendrimers

Cited by 14 publications

References 297 publications

Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Synthesis and Relaxometric Studies of a Dendrimer‐Based pH‐Responsive MRI Contrast Agent

Thermal behavior of metallodendrimers possessing bis(terpyridinyl)Ru(II) connectivity and different surface functionality

Comprehensive profiling of the complex dendrimeric contrast agent Gadomer using a combined approach of CE, MS, and CE‐MS

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Thermal behavior of metallodendrimers possessing bis(terpyridinyl)Ru^(II) connectivity and different surface functionality