The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of 188Re-herceptin.
The therapeutic efficacy of radioimmunotherapy (RIT) of 188Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with 188Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n = 3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of 188Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of 188Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of 188Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.
Li
Guiping
G
Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800, P.R. China. ligp@fimmu.com
Wang
Yongxian
Y
Huang
Kai
K
Zhang
Hui
H
Peng
Wuhe
W
Zhang
Chunfu
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001822:Body Burden; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015552:Injections, Intralesional; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D011874:Radiometry / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012062:Relative Biological Effectiveness; D012211:Rhenium / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D012211:Rhenium; D000068878:Trastuzumab