Iw. Kellaway et al., THE IN-VITRO CHARACTERIZATION AND BIOSTABILITY OF TC-99M-DEXTRAN AND ITS ACCUMULATION WITHIN THE INFLAMED PAWS OF ADJUVANT-INDUCED ARTHRITIC RATS, Pharmaceutical research, 12(4), 1995, pp. 588-593
The in vitro and in vivo stability in normal and adjuvant-induced arth
ritic rats of Tc-99-dextrans (10, 40 and 500 kDa) have been investigat
ed. The circulation half-lives were molecular weight dependent, with 1
0 and 40 kDa fractions being cleared relatively rapidly due to their a
bility to cross the glomerular basement membrane. The 500 kDa dextran
was eliminated more slowly although 79% had been removed from the circ
ulation 4 h post injection which probably was due to its degradation b
y dextranases and subsequent glomerular excretion. Dextran accumulatio
n by the RES was found to be similar for all molecular weight preparat
ions with no significant differences found. The sequestration of the d
extrans by tissues of the RES (liver, spleen and lung) was independent
of clearance rate. No differences were seen between normal and arthri
tic groups. Accumulation of the polymers by inflamed paws greatly exce
eded that of normal paws for the 10 kDa (5-fold) and 500 kDa (6-fold)
although no differences were seen with the 40 kDa dextran.