| Abstract | PURPOSE: 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 AND MATERIALS: 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. CONCLUSION: 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. |
| Authors | Jörgen Elgqvist, Håkan Andersson, Peter Bernhardt, Tom Bäck, Ingela Claesson, Ragnar Hultborn, Holger Jensen, Bengt R Johansson, Sture Lindegren, Marita Olsson, Stig Palm, Elisabet Warnhammar, Lars Jacobsson
(Affiliation: Department of Radiation Physics, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. jorgen.elgqvist at radfys.gu.se)
|
| Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 66
Issue 4
Pg. 1228-37
(Nov 15 2006)
ISSN: 1879-355X United States |
| PMID | 17145538
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antibodies, Monoclonal
- Radiopharmaceuticals
- Astatine
|
| Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Astatine
(therapeutic use)
- Data Interpretation, Statistical
- Dose Fractionation
- Female
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Ovarian Neoplasms
(pathology, radiotherapy, secondary)
- Radiation Dosage
- Radioimmunotherapy
(methods)
- Radiopharmaceuticals
(therapeutic use)
- Treatment Outcome
|
