Kinetics of 57Co-bleomycin in sheep after intra-arterial injection in the head and neck region.
Intra-arterial (i.a.) chemotherapy for the treatment of head and neck tumors is performed on the basis of clinical reports. The hypothetical aim of i.a. chemotherapy is to achieve higher drug concentrations in the tumor than are achieved by systemic intravenous (i.v.) administration. Therefore, it is postulated that i.a. chemotherapy leads to an increased therapeutic effect at the tumor site and to a decrease in systemic drug toxicity. The lack of adequate animal experiments and the absence of prospective randomized clinical trials comparing i.a. with i.v. chemotherapy led to the present kinetic study, concerned with various modes of administration of bleomycin with the aim of achieving high cytotoxic concentrations at the required site. Radioactive bleomycin (57Co-bleomycin) was injected locally (buccal plane, group I), intra-arterially (transverse facial artery, group II; superficial temporal artery, group III; external carotid artery, group IV), and intravenously (saphenous vein, group V) in five sheep per group. Between 1 and 360 min after injection of radioactive bleomycin the urine and the systemic blood activities were determined, and the activities in the hypothetical tumor area (buccal plane) were measured continuously. The animals were killed 360 min after injection and the activities in the hypothetical tumor area, in the lymph nodes draining this area (submandibular, parotic, lateral pharyngeal) and in different tissues and organs were determined. For all groups, 70%-80% of the injected bleomycin was eliminated by the kidneys, without any significant differences among the five groups tested. The systemic blood activities measured at 5-min intervals exhibited no differences for the groups injected i.a. (II-IV) and i.v. (V). Only animals which received local injections (group I) showed lower activities for 60 min after injection as compared with the other four groups. The activities of radioactively labeled bleomycin in the hypothetical tumor area during the entire experiment (360 min) were again similar for the groups injected i.a. (II-IV) and those injected i.v. (V). However, only animals injected locally (group I) showed significantly increased activities. After the death of the animals there was again no significant difference between i.a. and i.v. administration. Only local injection led to significantly increased tissue activities. Similar results also obtained for the lymph nodes draining the hypothetical tumor area.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D001761:Bleomycin / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy*; D007261:Infusions, Intra-Arterial / Q000379:methods*; D007700:Kinetics; D008198:Lymph Nodes / Q000378:metabolism; D008657:Metabolic Clearance Rate; D009061:Mouth Mucosa / Q000378:metabolism; D012756:Sheep
D001761:Bleomycin