Title:Targeted Alpha Therapy with 227Th-trastuzumab of Intraperitoneal Ovarian Cancer in Nude Mice
Volume: 6
Issue: 2
Author(s): Helen Heyerdahl, Nasir Abbas, Kristine Sponheim, Camilla Mollatt, Oyvind Bruland and Jostein Dahle
Affiliation:
Keywords:
Radioimmunotherapy, targeted alpha therapy, Thorium-227, trastuzumab, bioluminescence, alpha particle, ovarian
cancer.
Abstract: The aim of the current study was to investigate the therapeutic effect of 227Th-radioimmunotherapy on intraperitoneally
growing human bioluminescent HER2 positive ovarian cancer cells.
Methods: In vitro toxicity of 227Th-trastuzumab in bioluminescent SKOV3-luc-D3 ovarian cancer cells was assessed in a
growth assay. The biodistribution of intraperitoneally administrated 227Th-trastuzumab in athymic nude mice without tumor
cells was determined. For in vivo therapy, seventy female athymic nude mice were intraperitoneally inoculated with
tumor cells 17 days prior to injection of single 227Th-trastuzumab doses of 1000 kBq/kg, 600 kBq/kg or 400 kBq/kg, or
three injections with 400 kBq/kg 227Th-trastuzumab separated by 4 weeks. Two control groups were given either 20 µg
unlabeled trastuzumab or 0.9 % NaCl. In vivo bioluminescence imaging was performed weekly before and after onset of
therapy. Tumor growth, survival and toxicity were compared.
Results: There was a statistically significant therapeutic effect of the 227Th-trastuzumab treatment both with respect to
survival and tumor growth. The maximum tolerated dosage was 600 kBq/kg 227Th-trastuzumab. In the in vitro study, two
hours incubation with 20 kBq/ml of 227Th-trastuzumab, followed by washing, and subsequent culture of the cells resulted
in an average absorbed radiation dose of 6 Gy after 11 days and complete growth inhibition.
Conclusion: Targeted alpha therapy with 227Th-trastuzumab of human SKOV3-luc-D3 cells growing intraperitoneally in
nude mice was clearly superior to unlabeled trastuzumab therapy. The results warrant further studies of 227Thradioimmunotherapy
used as adjuvant treatment and for metastatic cancer.
