Abstract

Purpose: To evaluate a proof-of-concept framework for selecting chelators for retained heavy metals by integrating coordination-chemistry criteria with directly measured in vivo decorporation, using gadolinium (Gd) as the principal model metal and lead (Pb), cadmium (Cd), and mercury (Hg) as secondary comparators. Materials and methods : A 64-year-old White male who had received 15 gadoliniumbased contrast agent (GBCA) administrations between 1989 and 2014, without symptoms attributable to gadolinium toxicity, underwent four consecutive chelation administrations approximately one month apart, in the following order: oral HOPO, oral DOTA, intravenous (iv) Ca-DTPA, and oral Emeramide. The agents represented chemically distinct ligand classes and delivery characteristics. Chelator performance was interpreted using metalligand stability, kinetic and physiological accessibility, ability to form the complex under physiological conditions, route of administration, and directly measured change in 24-hour urinary metal elimination. For each agent, urine was collected 1–2 days before chelation and beginning within 1 hour after administration. Twenty potentially toxic metals were measured; Gd, Pb, Cd, and Hg were selected as representative metals. A threefold or greater increase from pre- to post-chelation was considered substantial. Results: Following iv Ca-DTPA, urinary Gd increased 164-fold, Pb 14.5-fold, Cd 20-fold, and Hg 4.1-fold. Following oral HOPO, urinary Gd increased 9.4-fold and Hg 5.1-fold. Oral DOTA and oral Emeramide produced no substantial increase in elimination of the four selected metals under the tested conditions. Conclusions: The findings support a staged method for chelator selection in which coordination chemistry identifies plausible candidates, but physiologically feasible complex formation and actual in vivo decorporation must also be demonstrated. In this enriched intra-individual model, iv Ca-DTPA produced the greatest removal of Gd, Pb, and Cd, whereas oral HOPO increased removal of Gd and Hg. The high retained-Gd burden amplified the urinary Gd signal and provided a sensitive test of the selection framework. Although Gd was the principal model metal, the methodology is potentially generalizable to other retained heavy metals and warrants evaluation in larger controlled studies.

Keywords

chelation, heavy metals, gadolinium, DTPA, coordination chemistry, decorporation