Repeated radioimmunotherapy with 177Lu-DOTA-BR96 in a syngeneic rat colon carcinoma model.
OBJECTIVE
Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration.


METHODS
Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose.


RESULTS
The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases.


CONCLUSIONS
In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity.
Department of Oncology, Lund University, Sweden. sophie.eriksson@med.lu.se
Sophie E
SE
Eriksson
Tomas
T
Ohlsson
Rune
R
Nilsson
Jan
J
Tennvall
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000528:radiation effects; D001835:Body Weight / Q000528:radiation effects; D002277:Carcinoma / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects; D007962:Leukocytes / Q000528:radiation effects; D008187:Lutetium / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D011914:Rats, Inbred BN
D000911:Antibodies, Monoclonal; C507851:BR96 monoclonal antibody; D018796:Immunoconjugates; D011868:Radioisotopes; D008187:Lutetium