Desferrioxamine-chelatable iron, a component of serum non-transferrin-bound iron, used for assessing chelation therapy

This study introduces a method for monitoring a component of serum non-tran sferrin-bound iron (NTBI), termed "desferrioxamine-chelatable iron" (DCI), It is measured with the probe fluorescein-desferrioxamine (FI-DFO), whose f luorescence is stoichiometrically quenched by iron. DCI was found in the se rum of most patients with thalassemia major (21 of 27 tested, range 1.5-8.6 muM), but only in a minority of patients with hereditary hemochromatosis ( 8 of 95 samples from 39 patients, range 0.4-1.1 muM) and in none of 48 cont rols, The method was applied to monitoring the appearance of iron in the se rum of patients under chelation therapy, Short-term (2 hours) follow up of patients immediately after oral administration of deferriprone (L1) showed substantial mobilization of DCI into the serum (up to 10 muM within 30-60 m inutes), The transfer of DCI from L1 to FI-DFO was observed in vitro with p reformed L1-iron complexes, and occurred even at L1/iron ratios exceeding 3 :1, Simultaneous administration of oral L1 and intravenous DFO to patients abrogated the L1-mediated rise in DCI, consistent with the shuttling of iro n from L1 to DFO in vivo. A similar iron transfer from L1 to apo-transferri n was observed in vitro, lending experimental support to the notion that L1 can shuttle iron in vivo to other high affinity ligands, These results pro vide a rationale for using chelator combinations, with the highly permeant L1 acting as an intracellular chelator-shuttle and the less permeant DFO se rving as an extracellular iron sink. Potential applications of the DCI assa y may be for studying chelator action and as an index of patient chelation status. (C) 2001 by The American Society of Hematology.