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Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.

Artikel i vetenskaplig tidskrift
Författare 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 Finnborg
Lars Jacobsson
Publicerad i International journal of radiation oncology, biology, physics
Volym 66
Nummer/häfte 4
Sidor 1228-37
ISSN 1879-355X
Publiceringsår 2006
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Institutionen för matematiska vetenskaper, matematisk statistik
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Institutionen för kliniska vetenskaper
Sidor 1228-37
Språk en
Länkar dx.doi.org/10.1016/j.ijrobp.2006.07...
Ämnesord 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
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

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.

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