Ablation of Colorectal Xenografts with Combined Radioimmunotherapy and Tumor Blood Flow-modifying Agents

摘要: Radioimmunotherapy (RIT) does not readily eradicate common solid tumors and therefore requires augmentation by complementary therapies that do increase normal tissue damage. We have examined the efficacy of RIT combined with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a drug which induces immunomodulation cytokine production preferentially reduces tumor blood flow, using colorectal xenograft model in nude mice. Although an optimal i.p. dose (27.5 mg/kg) alone induced massive hemorrhagic necrosis all but thin peripheral rim viable cells, survival was unaffected. However, when i.v. 18.5 MBq 131I-labeled anti-carcinoembryonic antigen IgG, DMXAA significantly potentiated without increased toxicity, five six mice showing complete cures. Scheduling critical because antibody must be allowed to reach maximum accumulation before initiation drug-induced flow inhibition. Subsequently, retained tumor, reaching approximately twice control levels 5 days after delivery. In studies, had narrow therapeutic window, 30 mg/kg being toxic two mice, whereas 20 were ineffective. addition second vasoactive agent, serotonin, plus enhanced therapy increasing systemic toxicity. Tumor histology phosphor image plate analysis reflected these results. When given RIT, drugs combined, although alone, also inhibited growth. Drug-induced retention radioantibody may both contribute produced this therapy.