Polymeric conjugates of Gd3+-diethylenetriaminepentaacetic acid and dextran.: 2.: Influence of spacer arm length and conjugate molecular mass on the paramagnetic properties and some biological parameters

被引:46
作者
Rebizak, R
Schaefer, M
Dellacherie, E
机构
[1] Ecole Natl Super Ind Chim, Inst Natl Polytech Lorraine, URA CNRS 494, Lab Chim Phys Macromol, F-54001 Nancy, France
[2] Guerbet GCA, F-93601 Aulnay Sous Bois, France
关键词
D O I
10.1021/bc9701499
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Macromolecular conjugates of dextran 40 ((M-n) over bar = 38 kg/mol, (M-w) over bar = 43 kg/mol) and diethylenetriaminepentaacetic acid (DTPA), capable of complexing Gd3+, were synthesized in order to obtain contrast agents for nuclear magnetic resonance imaging, with long intravascular persistence. As already reported, relaxivity of these macromolecular complexes was greater than that of molecular complexes (2-2.5 times). On the other hand, as relaxivity of paramagnetic agents partially depends on their rotation speed, the influence of the length of the spacer arm inserted between DTPA and dextran was investigated. Various conjugates with spacer arms comprised of methylenic chains (-(CH2)(n)-) with varying lengths (2 less than or equal to n less than or equal to 6) were prepared. The result was that, whatever the distance between DTPA and dextran, all of the Gd3+-complexed polymeric conjugates with similar DTPA content (0.6-0.8 mmol/g) exhibited, at 20 MHz, about the same relaxivity values. On the other hand, in the same way, no significant effect of the molecular masses ((M-n) over bar between 166 and 224 kg/mol and (M-w) over bar between 332 and 865 kg/mol) of the polymeric conjugates on relaxivity were observed. Toxicity studies carried out on mice, showed very similar LD50 values whatever the spacer arm and molecular mass of the macromolecular conjugates. Finally the urinary excretion studied on rats (after 4 h) and on rabbits (after 24 h) was relatively low (15-20% of the administered dose), and, as expected, the lower values were obtained with the higher molecular mass conjugates.
引用
收藏
页码:94 / 99
页数:6
相关论文
共 29 条
[1]   SYNTHESIS AND NMRD STUDIES OF GD3+ COMPLEXES OF MACROCYCLIC POLYAMINO POLYCARBOXYLIC LIGANDS BEARING BETA-BENZYLOXY-ALPHA-PROPIONIC RESIDUES [J].
AIME, S ;
BOTTA, M ;
ERMONDI, G .
INORGANIC CHEMISTRY, 1992, 31 (06) :1100-1103
[2]   SYNTHESIS, CHARACTERIZATION, AND 1/T(1) NMRD PROFILES OF GADOLINIUM(III) COMPLEXES OF MONOAMIDE DERIVATIVES OF DOTA-LIKE LIGANDS - X-RAY STRUCTURE OF THE 10-[2-[[2-HYDROXY-1-(HYDROXYMETHYL)ETHYL]AMINO]-1-[(PHENYLMETHOXY)METHYL]-2-OXO-ETHYL]-1,4,7,10-TETRAAZACYCLODODECANE-1,4,7-TRIACETIC ACID GADOLINIUM(III) COMPLEX [J].
AIME, S ;
ANELLI, PL ;
BOTTA, M ;
FEDELI, F ;
GRANDI, M ;
PAOLI, P ;
UGGERI, F .
INORGANIC CHEMISTRY, 1992, 31 (12) :2422-2428
[3]   Polymeric Contrast Agents for Magnetic Resonance Imaging: Synthesis and Characterization of Gadolinium Diethylonetriaminepentaacetic Acid Conjugated to Polysaccharides [J].
Armitage, Frances E. ;
Richardson, David E. ;
Li, King C. P. .
BIOCONJUGATE CHEMISTRY, 1990, 1 (06) :365-374
[4]   USE OF PARAMAGNETIC CHELATED METAL DERIVATIVES OF POLYSACCHARIDES AND SPIN-LABELED POLYSACCHARIDES AS CONTRAST AGENTS IN MAGNETIC-RESONANCE-IMAGING [J].
BLIGH, SWA ;
HARDING, CT ;
SADLER, PJ ;
BULMAN, RA ;
BYDDER, GM ;
PENNOCK, JM ;
KELLY, JD ;
LATHAM, IA ;
MARRIOTT, JA .
MAGNETIC RESONANCE IN MEDICINE, 1991, 17 (02) :516-532
[5]  
BLOCH F, 1946, PHYS REV, V70, P460, DOI 10.1103/PhysRev.70.460
[6]  
BLOEMBERGEN N, 1948, PHYS REV, V73, P678
[7]   RATIONALE AND APPLICATIONS FOR MACROMOLECULAR GD-BASED CONTRAST AGENTS [J].
BRASCH, RC .
MAGNETIC RESONANCE IN MEDICINE, 1991, 22 (02) :282-287
[8]  
Dellacherie E., 1996, POLYSACCHARIDES MED, P525
[10]   NEW COMPOUNDS - FATTY-ACID AND LONG-CHAIN HYDROCARBON DERIVATIVES CONTAINING A STRONG CHELATING AGENT [J].
ECKELMAN, WC ;
KARESH, SM ;
REBA, RC .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1975, 64 (04) :704-706