Endolymphatic application of bleomycin oil suspension in dog model

To explore the potential usefulness of a cytostatic agent deposited directly in lymph nodes, 4ml Bleomycin oil suspension (Oil-Bleo) was injected over one hour into hind leg lymphatics of seven dogs. Five of these dogs received a second, identical dose one week later into lymphatics of the contralateral hind leg. Peak serum concentration of Oil-Bleo after the first injection (7 dogs) was 12.3 micrograms/ml but after the second injection (5 dogs) was slightly lower (10.8 micrograms/ml). Maximum level of Oil-Bleo in blood was 12% of the endolymphatic dose and represented the "spillover" from lymph transport. In a control experiment, in which 60mg of aqueous Bleomycin was injected, the serum spillover was one-third higher. Large amounts of Oil-Bleo were stored in popliteal and retroperitoneal lymph nodes for several weeks. Twenty-four hours after injection the weight of "treated" lymph nodes was 73% greater than "untreated" nodes and one month later treated lymph nodes were still 37% heavier. After 24 hours, 4.7% of Oil-Bleo instilled was distributed within extracted lymph nodes, and one month later 0.12% was still detectable. By contrast, after aqueous Bleomycin infusion, only 0.05% was detected in these lymph nodes after only six hours. In general, lymph nodal architecture was preserved after Oil-Bleo. Together the findings suggest that Bleomycin oil suspension may be a useful agent for treatment of lymph nodal metastases by endolymphatic infusion.