Gadolinium-containing copolymeric chelates - A new potential MR contrast agent

Evan C Unger, Dekang Shen, Guanli Wu, Leah Stewart, Terry O Matsunaga, Theodore "Ted" Trouard

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents. Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers. Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. The r1 (1/T1, mM-1 s-1) for Gd-DTPA = 4.1. The r1 values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowest r1 for the polymer prepared with the lowest- molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd- DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement - a reflection of distribution into extravascular fluid space - was observed. Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd- DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase in r1 relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd- copolymers are promising agents that merit additional study.

Original languageEnglish (US)
Pages (from-to)154-162
Number of pages9
JournalMagnetic Resonance Materials in Physics, Biology and Medicine
Volume8
Issue number3
DOIs
StatePublished - Aug 1999

Fingerprint

Gadolinium
Contrast Media
Pentetic Acid
Magnetic Resonance Spectroscopy
Gadolinium DTPA
Blood Vessels
Molecular Weight
Angiography
Polymers
Rabbits
Magnetic Resonance Angiography
Weights and Measures

Keywords

  • Blood pool
  • Chelates
  • Gadolinium
  • MR contrast agents
  • Polymers

ASJC Scopus subject areas

  • Biophysics
  • Genetics

Cite this

Gadolinium-containing copolymeric chelates - A new potential MR contrast agent. / Unger, Evan C; Shen, Dekang; Wu, Guanli; Stewart, Leah; Matsunaga, Terry O; Trouard, Theodore "Ted".

In: Magnetic Resonance Materials in Physics, Biology and Medicine, Vol. 8, No. 3, 08.1999, p. 154-162.

Research output: Contribution to journalArticle

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abstract = "Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents. Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers. Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2{\%} on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. The r1 (1/T1, mM-1 s-1) for Gd-DTPA = 4.1. The r1 values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowest r1 for the polymer prepared with the lowest- molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd- DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement - a reflection of distribution into extravascular fluid space - was observed. Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd- DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50{\%} increase in r1 relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd- copolymers are promising agents that merit additional study.",
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AU - Trouard, Theodore "Ted"

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N2 - Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents. Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers. Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. The r1 (1/T1, mM-1 s-1) for Gd-DTPA = 4.1. The r1 values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowest r1 for the polymer prepared with the lowest- molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd- DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement - a reflection of distribution into extravascular fluid space - was observed. Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd- DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase in r1 relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd- copolymers are promising agents that merit additional study.

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