Pharmacokinetics of bleomycin in man - III. Bleomycin ⁵⁷Co Vs Bleomycin

Of all the bleomycin-containing radiopharmaceuticals, bleomycin ⁵⁷Co has proven the most useful whole-body tumor-imaging agent. We have studied its in vitro physicochemical properties and in vivo disposition in animals and man to optimize its use as a scanning agent. High-pressure liquid chromatographic analysis of the standard bleomycin ⁵⁷Co preparation (1 unit bleomycin plus 1 mCi chloride ⁵⁷Co showed it to contain 1% free chloride ⁵⁷Co). Dialysis experiments showed that bleomycin ⁵⁷Co does not dissociate as it diffuses through a dialysis membrane. In nine patients, bleomycin ⁵⁷Co had a t₁^2/βof 3.4 h, a t₁^2/γof 45.8 h, a V_d of 12.1 liters/m² and a 24-h urinary excretion of 82.1% of the administered dose. In comparison, bleomycin, assayed by radioimmunoassay, had a terminal phase plasma t_1/2 of only 4.0 h, a similar V_d (17.3 liters/m²), and a 24-h urinary excretion of only 44.8%. Bleomycin ⁵⁷Co tumorto-plasma concentration ratios ranged from 14.1-23.8 at 1 day to 5.4 at 2 days after administration. Our finding that tumor imaging with bleomycin ⁵⁷Co is best achieved at 24 h is well explained by its almost complete urinary elimination in the first few hours after administration and the peak tumor-to-plasma ratio achieved at 24 h. One disadvantage of bleomycin ⁵⁷Co as a scanning agent is its very extended plasma t_1/2 In rabbits chloride ⁵⁷Co has the same prolonged plasma terminal elimination phase (t₁^2/γ) as our standard bleomycin ⁵⁷Co preparation, which contains chloride ⁵⁷Co as a 1% impurity. Removal of this impurity prior to scanning or use of cold cobalt chloride to help eliminate it from the plasma might result in a shortened bleomycin ⁵⁷Co plasma t₁^2/γ.