Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
OBJECTIVE
To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2.


METHODS
Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF).


RESULTS
When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy.


CONCLUSIONS
As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.
Elgqvist
Jörgen
J
Department of Radiation Physics, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. jorgen.elgqvist@radfys.gu.se
Andersson
Håkan
H
Bernhardt
Peter
P
Bäck
Tom
T
Claesson
Ingela
I
Hultborn
Ragnar
R
Jensen
Holger
H
Johansson
Bengt R
BR
Lindegren
Sture
S
Olsson
Marita
M
Palm
Stig
S
Warnhammar
Elisabet
E
Jacobsson
Lars
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001246:Astatine / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D019583:Dose Fractionation, Radiation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D011829:Radiation Dosage; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D001246:Astatine