Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose.
Artikel i vetenskaplig tidskrift, 2006

The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. METHODS: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with approximately 400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. RESULTS: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340 mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35, approximately 4, and approximately 0.3 Gy, respectively. CONCLUSION: Treatment with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100% when the tumor radius was < or =30 microm. The TFF was decreased (TFF 22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.

Tumor

Mice

Cell Line

Mice

Alpha Particles

Treatment Outcome

methods

therapeutic use

therapeutic use

Radioimmunotherapy

therapy

Electron

Antibodies

Microscopy

Monoclonal

Ovarian Neoplasms

Female

Animals

Antineoplastic Agents

Mice

Nude

Neoplasm Transplantation

Humans

Inbred BALB C

radionuclide imaging

Författare

Jörgen Elgqvist

Göteborgs universitet

Håkan Andersson

Göteborgs universitet

Tom Bäck

Göteborgs universitet

Ingela Claesson

Göteborgs universitet

Ragnar Hultborn

Göteborgs universitet

Holger Jensen

Bengt R Johansson

Göteborgs universitet

Sture Lindegren

Göteborgs universitet

Marita Olsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Stig Palm

Göteborgs universitet

Elisabet Warnhammar Finnborg

Göteborgs universitet

Lars Jacobsson

Göteborgs universitet

Journal of Nuclear Medicine

0161-5505 (ISSN)

Vol. 47 8 1342-50

Ämneskategorier

Cell- och molekylärbiologi

NATURVETENSKAP

PubMed

16883015

Mer information

Skapat

2017-10-06