1.
Andersson, Håkan, 1944
(författare)
Radioimmunotherapy of experimental ovarian cancer with Astatine-211. An in vivo model for consolidation treatment in women
2000
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
About 850 new cases of ovarian cancer are diagnosed in Sweden every year. In 75 % of the patients the tumour has spread outside the ovaries. The standard treatment is surgery followed by six courses of combination chemotherapy. In spite of a very high frequency of clinical complete responses the 5-year survival is not satisfactory. Thus there is a great need for consolidating therapy.Radioimmunotherapy (RIT), i.e. treatment with specific monoclonal antibodies (MAb) labelled with radionuclides has been tried for various tumours experimentally and clinically. In most studies b-emitters have been used but for micrometastases an a-emitter with a very short tissue range may be better.The purpose of this study was to examine the in vitro effect of the a-emitter Astatine-211 (211At) and to investigate the therapeutic efficacy of regional administration of the specific antibody MOv18 labelled with 211At to nude mice with intraperitoneal growth of human ovarian cancer. Methods. For the in vitro studies the two human cancer cell lines NIH:OVCAR-3 and Colo-205 were used. Cell suspensions were treated with free 211At, 211At-albumin, 211At-Mab or with photon irradiation. The human ovarian cancer cell line NIH:OVCAR-3 was used for the in vivo studies. Two weeks after the inoculation of cells, when the tumour still was microscopic, 211At-MOv18 was injected intraperitoneally. The therapeutic effect was evaluated six weeks later except in the long-term studyResults. In vitro the uptake of free 211At on both cell lines was unexpectedly high. A low number (19-31) of 211At decays on the cell surface was needed for 37% cell survival for both cell types.In the short term in vivo studies 18 of 20 mice were tumour-free when 211At-MOv18 was injected i.p. In the long-term study the survival was significantly better for treated than for untreated mice. Thirty-three per cent of the animals were tumour-free at the end of the study.Conclusion. Intraperitoneal radioimmunotherapy with an 211At-labelled specific antibody is an effective treatment of human ovarian cancer growing in nude mice. Hopefully, this treatment will be of value as consolidating treatment in women with minimal residual disease after surgery and chemotherapy
2.
Palm, Stig, 1964, et al.
(författare)
Cell growth kinetics of the human cell line Colo-205 irradiated with photons and astatine-211 alpha-particles
2000
Ingår i: Anticancer Res. - 0250-7005. ; 20:3A, s. 1807-12
Tidskriftsartikel (refereegranskat) abstract
Cell growth kinetics following Astatine-211 (211At, alpha-particle emitter) and photon irradiation were studied for the human colorectal cell line Colo-205. A growth assay using 96-well plates was chosen. The growth kinetics could be simulated by assuming certain fractions of cells with various proliferative capacities, i.e. from none up to 5 cell doublings, in addition to the defined survivors with remaining unlimited clonogenic capacity. No significant difference in cell growth characteristics was seen between 211At and photon irradiation. The cell doubling time, as calculated from the increment in optical density, was compared with the results from BrdU experiments in the early phases of growth (Tpot = 18.5 +/- 0.6 h for LDR (low dose rate) photon irradiated and 20.3 +/- 0.8 hours for sham-irradiated cells 40-45 hours post-irradiation) confirming the transient accelerated growth of irradiated cells. No statistically significant difference in growth was found between LDR, MDR (medium dose rate) and HDR (high dose rate) photon irradiation.
3.
Palm, Stig, 1964, et al.
(författare)
In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines
2000
Ingår i: Anticancer Res. - 0250-7005. ; 20:2A, s. 1005-12
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: The aim of this study was to perform various 211At irradiations of importance for the evaluation of 211At-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation. MATERIALS AND METHODS: All irradiations were performed on low-concentration single-cell suspensions. Growth assays using 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of 211At. RESULTS: A relative biological effect (RBE) of 12 +/- 2 (Colo-205) and 5.3 +/- 0.7 (OVCAR-3) was found from 211At-albumin irradiations. There was a 174 +/- 28 times higher free 211At concentration in the cell fraction than in the surrounding medium. For 211At-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achieved, compared to the medium. Corrected for the uptake, an average of 31 +/- 2 ([211At]-astatine) or 26 +/- 5 ([211At]-MAb) decays per cell were required for 37% survival of Colo-205 cells. An average of 19 +/- 3 decays ([211At]-astatine) were required per OVCAR-3 cell. CONCLUSIONS: Cell uptake and binding of 211At was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3 +/- 0.7 for OVCAR-3 and 12 +/- 2 for Colo-205 cells.
