To evaluate the ability of an anti-placental alkaline phosphatase (PLAP) monoclonal antibody (MAb) to localize to PLAP-expressing tumors, we established a model of testicular tumor with metastasis to lymph nodes and liver in severe combined immunodeficient (SCID) mice. 131I-labeled or 125I-labeled MAb was simultaneously administered via the intravenous or lymphatic route, respectively. Preferential accumulation of MAb in PLAP-expressing tumors at primary as well as metastatic sites was demonstrated. The percentage of the injected dose of MAb found in the tumor was generally higher when MAb was administered intravenously. Identical tumor/blood ratios were found with the two routes of administration. These data suggest that intravenous administration of a radiolabeled MAb is superior to lymphatic administration for tumor imaging and radioimmunotherapy.