Preclinical evaluation and phase I clinical trial of a 99mTc-labeled synthetic polymer used in blood pool imaging.

To obtain initial data on the safety and efficacy of a novel polymeric, synthetic blood pool contrast agent [O-monomethoxypoly(ethylene glycol)-O'succinyl]poly(N-epsilon-L-lysyl [99mTc]diethylenetriamine pentaacetate monoamide, we performed a preclinical evaluation and phase 1 clinical trial under an investigator-sponsored investigational new drug application.Methoxypoly(ethylene glycol)ethylenetriaminopentaacetic acid was formulated into a kit containing the polymer, stannous chloride, and a buffer. Kits were stored in frozen form for subsequent labeling with technetium-99m. Acute and subacute toxicity studies were carried out in rats and rabbits. Healthy human volunteers (n = 6) were then enrolled in a prospective, open-label phase 1 clinical study.Animal studies showed no signs of acute or subacute toxicity at doses 280 times the proposed dose for humans. In the clinical trial with humans, no significant abnormalities of laboratory values, ECG findings, or hemodynamic parameters were seen. One voluntee...