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Curr Radiopharm. 2013 Jun 6;6(2):78-86.

Comparing high LET 227Th- and low LET 177Lu-trastuzumab in mice with HER-2 positive SKBR-3 xenografts.

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Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.


The aim of the present study was to compare the biodistribution, normal tissue toxicity and therapeutic effect of the alpha-particle emitting 227Th-trastuzumab and the beta-particle emitting 177Lu-trastuzumab in mice with HER2- expressing SKBR-3 breast cancer xenografts.


Biodistributions of the two radioimmunoconjugates were determined at different time points after i.v. injection. Inhibition of tumor growth was measured after single injection of 227Th-trastuzumab (200, 400, 600 or 1000 kBq/kg), 177Lu-trastuzumab (40 or 200 MBq/kg) or saline. The toxicity profiles were compared by measurements of body weight,clinical chemistry and hematological parameters, as well as histological examination of tissue specimens.


400 kBq/kg of 227Th-trastuzumab and 40 MBq/kg of 177Lu-trastuzumab both resulted in an absorbed radiation dose to tumor of approximately 3 Gy. A significant anti-tumor effect and increased survival were observed at injected dosages of 400-1000 kBq/kg of 227Th-trastuzumab and 200 MBq/kg of 177Lu-trastuzumab as compared to the saline control. When compared at the same therapeutic effect level (100% prolonged growth delay as compared to control) the absorbed radiation dose of 227Th-trastuzumab was 3 times lower than with 177Lu-trastuzumab, indicating a relative biological effect (RBE) of 2.8 for 227Th-trastuzumab. In contrast, when compared at the same temporary decrease of WBC count (50% decrease in number of white blood cells as compared to control), the growth delay was 3 times longer with 177Lutrastuzumab than with 227Th-trastuzumab, which indicates that the therapeutic index was three times higher for 177Lutrastuzumab than for 227Th-trastuzumab.


In this xenograft model the RBE was higher for 227Th-trastuzumab than for 177Lu-trastuzumab, while the therapeutic index of 177Lu-trastuzumab was superior to that of 227Th-trastuzumab.

[Indexed for MEDLINE]

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