The in vitro characterization and biostability of 99mTc-dextran and its accumulation within the inflamed paws of adjuvant-induced arthritic rats.
The in vitro and in vivo stability in normal and adjuvant-induced arthritic rats of 99mTc-dextrans (10, 40 and 500 kDa) have been investigated. The circulation half-lives were molecular weight dependent, with 10 and 40 kDa fractions being cleared relatively rapidly due to their ability to cross the glomerular basement membrane. The 500 kDa dextran was eliminated more slowly although 79% had been removed from the circulation 4 h post injection which probably was due to its degradation by dextranases and subsequent glomerular excretion. Dextran accumulation by the RES was found to be similar for all molecular weight preparations with no significant differences found. The sequestration of the dextrans by tissues of the RES (liver, spleen and lung) was independent of clearance rate. No differences were seen between normal and arthritic groups. Accumulation of the polymers by inflamed paws greatly exceeded 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.
Kellaway
I W
IW
Welsh School of Pharmacy, University of Wales College of Cardiff, United Kingdom.
Seale
L
L
Spencer
P S
PS
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D003911:Dextrans / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D005260:Female; D008657:Metabolic Clearance Rate; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003911:Dextrans; D015609:Organotechnetium Compounds; C034146:technetium Tc 99m dextran