Blood supply and drug delivery to primary and secondary human liver cancers studied with in vivo bromodeoxyuridine labeling

Abstract

Background: Because bromodeoxyuridine (BrdU) is incorporated into DNA synthesizing (S-phase) cells, the blood supply of liver tumors can be traced by injecting BrdU into either the hepatic artery or portal vein. It also is possible to study the delivery of anti-cancer drugs acting during S-phase when they are injected by these routes. The blood supply of and drug delivery to liver tumors were examined using BrdU in patients with 19 metastatic liver cancers and 8 hepatocellular carcinomas.

Methods: At the time of hepatic resection, 200 mg of BrdU was injected by the various routes or 200 mg of BrdU suspended in 2 ml of a lipid contrast medium was injected into the hepatic artery by a reported method 2 weeks before hepatectomy. The liver tumors resected were stained immunohistochemically with an avidin-biotin-peroxidase complex method using anti-BrdU monoclonal antibody.

Results: BrdU injected into the hepatic artery or portal vein was incorporated into the metastatic liver tumor. After intraarterial infusion BrdU suspension, the delivery of BrdU was enhanced. The nuclei of hepatocellular carcinomas that received BrdU from the hepatic artery or portal vein incorporated BrdU.

Conclusions: Metastatic liver cancers had both arterial and portal blood supplies. Hepatocellular carcinomas also had, not only an arterial, but also a portal blood supply. In both primary and secondary hepatic cancers, the delivery of anti-cancer agents acting during S-phase using the lipid contrast medium administration method was excellent.