177Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to 213Bi-immunotherapy, but causes toxicity not observed with 213Bi

Abstract Purpose 213Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the β-emitter 177Lu has proven to be beneficial in targeted therapy, 177Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of 213Bi-d9MAb. Methods Nude mice were inoculated intraperitoneally with HSC45-M2 gastric cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8 days later with different activities of specific 177Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific 177Lud8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of 177Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Results Treatment with 177Lu-immunoconjugates (1.85, 7.4, 14.8 MBq) significantly prolonged survival. As expected, treatment on day 1 after tumour cell inoculation was more effective than treatment on day 8, and specific 177Lu-d9MAb conjugates were superior to nonspecific 177Lu-d8MAb. Treatment with 7.4 MBq of 177Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of 177Lu-d9MAb was not free of toxic side effects. In some animals lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were seen but were not observed after treatment with 213Bid9MAb at comparable therapeutic efficacy. Conclusion The therapeutic efficacy of 177Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with 213Bid9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis.

SEIDL C.;  ZÖCKLER C;  BECK R.;  QUINTANILLA-MARTINEZ L;  BRUCHERTSEIFER Frank;  SENEKOWITSCH-SCHMIDTKE R.; 

2011-07-12

SPRINGER

JRC65531

1619-7070,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC65531,   

10.1007/s00259-010-1639-2,