[Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging].
OBJECTIVE
To study the mechanism of cardiotoxicity associated with Herceptin.


METHODS
Herceptin 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.


RESULTS
The 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).


CONCLUSIONS
Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.
Fan
Yi-xiang
YX
Department of Nuclear Medicine, Second People's Hospital of Guangdong Province, Guangzhou 510317, China. fanyix06@sohu.com
Luo
Rong-cheng
RC
Gao
Mei-ju
MJ
Liu
Qing-zhu
QZ
Li
Ke-bin
KB
Wu
Ji-zhen
JZ
Shi
Wei-min
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D016719:Radioimmunodetection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014018:Tissue Distribution; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007457:Iodine Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab