Gadolinium-containing copolymeric chelates--a new potential MR contrast agent.
OBJECTIVE
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.
Unger
E C
EC
ImaRx Pharmaceutical Corporation, Tucson, AZ 85719, USA.
Shen
D
D
Wu
G
G
Stewart
L
L
Matsunaga
T O
TO
Trouard
T P
TP
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000031:analogs & derivatives* / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D018810:Magnetic Resonance Angiography / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008970:Molecular Weight; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D014867:Water / Q000737:chemistry
D002614:Chelating Agents; D003287:Contrast Media; D011108:Polymers; D011409:Propylene Glycols; C508052:gadolinium (DTPA-bis(aminoethoxy)etane) polymer; D014867:Water; C012504:polypropylene glycol; D011092:Polyethylene Glycols; D004369:Pentetic Acid; D019786:Gadolinium DTPA