Bisquaternary ammonium compounds as potential tumor imaging agents

Abstract

Reports of rapid accumulation of 3H- or 14C-labelled hexamethonium in cartilaginous tissues after intravenous administration to rats and mice and of binding of hexamethonium to chondroitin sulfate in vitro prompted synthesis of radioiodinated analogs of hexamethonium. Tissue distribution studies in rats performed at 0.5 and 2 h after intravenous administration of 14C-hexamethonium confirmed the propensity of this drug to accumulate in cartilaginous tissues. Tissue distribution studies were performed in both normal and chondrosarcoma tumor-bearing rats at 0.5 and 2 h after intravenous administration of the radioiodinated analogs. The radioiodinated analogs showed profiles of distribution of radioactivity comparable to that of hexamethonium. Levels of uptake were highest in kidney and urine at all time periods studied. High levels of activity were seen in trachea, intervertebral discs and, when present, tumor. A rapid dispersal of a relatively low level of radioactivity was seen in most other tissues and was followed by rapid clearance in all tissues except meninges which continued to accumulate radioactivity for as long as 2 h. A chondrosarcoma tumor was successfully imaged in a rat 15 min following intravenous administration of a radioiodinated analog of hexamethonium.