Abstract: Objective To evaluate the effect of radioimmunotherapy with 188Re-labeled herceptin in nude mice bearing nasopharyngeal carcinoma expressing HER2/neu proto-oncogene and explore the feasibility of 188Re-herceptin for use as a chemical therapeutic and radioimmunotherapeutic agent. Methods A direct radiolabeling method was used to prepare 188Re-Herceptin. Thirty-two nude mice bearing nasopharyngeal carcinoma were randomized into 4 groups (n=8) to receive single intravenous injection of 188Re-Herceptin, intratumoral injection of 188Re-Herceptin, 188Re-nmIgG and 188Re, respectively, all at the equivalent dose of 11.1 MBq (50 μl). Another 5 tumor-bearing mice received only intratumoral injection of 50 μl normal saline to serve as the control group. Two days after the injections, 3 mice were selected from each group (except for the control group) for biodistribution observation, and the rest mice were monitored for 4 consecutive weeks for tumor volume changes. Pathological examination of the tumor tissues was also performed. Results The radioactivity uptake in the tumor was significantly greater whereas normal organ uptake significantly lower in the nude mice receiving intratumoral 188Re-Herceptin injection than in those with intravenous 188Re-Herceptin injection (11.53%ID/g vs 2.79%ID/g at 48 h). Intratumoral 188Re-Herceptin injection caused greater inhibition of tumor growth at the 4th week as compared to the intravenous administration. Conclusions Intratumoral 188Re-Herceptin administration can significantly inhibit the development of nasopharyngeal carcinoma in mice, and may potentially serve as a new clinical option of regional therapy for treating nasopharyngeal carcinoma overexpressing HER2/neu.