Use of vasoactive agents to increase tumor perfusion and the antitumor efficacy of drug-monoclonal antibody conjugates

Abstract

The effects of both α1- and β-adrenergic blocking agents on the vascular perfusion of tumors were studied with the ultimate goal of improving diagnosis and therapy of solid tumors with the use of monoclonal antibody (MAb) conjugates. With the use of a subcutaneously growing murine thymoma, it was demonstrated that nonselective and cardioselective β-adrenergic blocking agents were capable of increasing threefold tumor-to-blood and tumor-to-liver perfusion of 125I-labeled MAbs. Subsequently, these β-adrenergic blocking agents were found to increase the antitumor efficacy of idarubcin (Ida)-MAb conjugates. Conjugate-treated mice that also received β-adrenergic blocking agents had a smaller mean..