Suppression of Tumor Vascular Activity by Radioantibody Therapy: Implications for Multiple Cycle Treatments

Abstract

Autoradiographic analysis of the intratumor location of radioiodinated Mu-9 anti-CSAp antibody within 7 days of administration reveals a restricted distribution within 3-6 cell layers surrounding tumor vessels. Within 7-14 days after suboptimal radioantibody treatment (∼3000 rads), tumor vessel morphology and physiology are altered. Vessel number is reduced by 60-70%, vessel diameter is reduced, and remaining vessels are surrounded by fibrotic tissue. Vascular volume (vv) is reduced by 75%, blood flow rate (BF) is reduced 65%, and vascular permeability (VP) to an lgG is reduced by 60%. The change in vv is reversible by day 35 but BP and VP remain suppressed. Normal tissue (liver and lung) vasculature experience only small pertubations in physiology. These functional changes in tumor vessels reduce the magnitude of accretion of a second dose of radioantibody in tumor but not in normal tissue.