Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging.
- Author:
Yi-xiang FAN
1
;
Rong-cheng LUO
;
Mei-ju GAO
;
Qing-zhu LIU
;
Ke-bin LI
;
Ji-zhen WU
;
Wei-min SHI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antibodies, Monoclonal; administration & dosage; pharmacokinetics; toxicity; Antibodies, Monoclonal, Humanized; Female; Iodine Radioisotopes; administration & dosage; pharmacokinetics; Male; Myocardium; metabolism; Rabbits; Radioimmunodetection; Receptor, ErbB-2; metabolism; Tissue Distribution; Trastuzumab
- From: Journal of Southern Medical University 2009;29(12):2477-2484
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the mechanism of cardiotoxicity associated with Herceptin.
METHODSHerceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues.
RESULTSThe O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).
CONCLUSIONMyocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.
