| 1. |
|
|
| 2. |
- Bäck, Tom, 1964, et al.
(author)
-
211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo
- 2005
-
In: J Nucl Med. - 0161-5505. ; 46:12, s. 2061-7
-
Journal article (peer-reviewed)abstract
- The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. METHODS: GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves, the doses required for a GI of 0.37 (D37) were derived, and the RBE of 211At was calculated. RESULTS: The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. CONCLUSION: Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.
|
|
| 3. |
|
|
| 4. |
- Elgqvist, Jörgen, 1963, et al.
(author)
-
Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')2: therapeutic efficacy and myelotoxicity
- 2006
-
In: Nucl Med Biol. - : Elsevier BV. - 0969-8051. ; 33:8, s. 1065-72
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. METHODS: Animals were intraperitoneally inoculated with approximately 1x10(7) cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with approximately 800, 3x approximately 267, approximately 400, 3x approximately 133, approximately 50 or 3x approximately 17 kBq (211)At-MX35 F(ab')(2) (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab')(2) (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the (211)At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the (211)At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the alpha-particles emitted by (211)At in the bone marrow. RESULTS: The tumor-free fractions of animals were 56% and 41% when treated with approximately 800 kBq and 3x approximately 267 kBq (211)At-MX35 F(ab')(2), respectively; 39% and 28% when treated with approximately 400 kBq and 3x approximately 133 kBq (211)At-MX35 F(ab')(2), respectively; and 17% and 22% when treated with approximately 50 kBq or 3x approximately 17 kBq (211)At-MX35 F(ab')(2), respectively. The nadir of the white blood cell (WBC) counts was decreased (from 46% to 19%, compared with the baseline WBC counts) and delayed (from Day 4 to Day 11 after the first injection) during the fractionated treatment compared with the single-dose treatment. The percentage of injected activity per gram (%IA/g) for blood, bone and bone marrow all peaked 6 h after injection at 13.80+/-1.34%IA/g, 4.00+/-0.69%IA/g and 8.28+/-1.38%IA/g, respectively. The BBLR and BMBLR were 0.20+/-0.04 and 0.58+/-0.01, respectively. The mean absorbed dose to bone marrow was approximately 0.4 Gy after intraperitoneally injecting approximately 800 kBq (211)At-MX35 F(ab')(2). CONCLUSION: No advantage was observed in the therapeutic efficacy of using a fractionated regimen compared with a single administration, with the same total amount of administered activity. Alleviation of the myelotoxicity was observed during the fractionated regimen in terms of decreased suppression and delayed nadir of the WBC counts. No thrombocytopenia was observed during either regimen.
|
|
| 5. |
- Elgqvist, Jörgen, 1963, et al.
(author)
-
Therapeutic efficacy and tumor dose estimations in radioimmunotherapy of intraperitoneally growing OVCAR-3 cells in nude mice with (211)At-labeled monoclonal antibody MX35
- 2005
-
In: J Nucl Med. - 0161-5505. ; 46:11, s. 1907-15
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the therapeutic efficacy of-and to estimate the absorbed dose to-tumor cells from radioimmunotherapy (RIT) in an ovarian cancer model using the alpha-particle-emitting nuclide (211)At labeled to monoclonal antibody (mAb) MX35. Previous studies on mAb MOv18 did not allow for dosimetry because of antigen shedding in vitro. METHODS: Five-week-old female nude BALB/c nu/nu mice were inoculated intraperitoneally with 1 x 10(7) cells of the human tumor cell line OVCAR-3. Three weeks later, the animals were given approximately 400, 800, or 1,200 kBq of (211)At-labeled mAb MX35 intraperitoneally. As controls, one group of animals was injected with unlabeled mAb and another group was injected with phosphate-buffered saline (PBS). Another group was given approximately 400 kBq of (211)At labeled to the previously investigated mAb MOv18 for efficacy comparison. Two months after treatment, the animals were sacrificed and the presence of macroscopic and microscopic tumors, as well as ascites, was determined. The absorbed dose to tumor cells on the peritoneal surface was estimated in terms of the sum of a specific and a nonspecific contribution. The specific contribution, arising from mAbs binding to the antigenic sites on the cell membrane, was calculated using a dynamic compartment model developed in-house and Monte Carlo software. The model used as input values the number of mAbs injected into the abdominal cavity, N(mAb), the specific activity, A(sp), the association rate constant, k(on), and the maximal number of mAbs bound per cell, B(max)-all determined by in vitro experiments. This specific component of the absorbed dose was calculated for assumed cell cluster sizes with radii of 25, 50, and 100 microm. The nonspecific contribution to the absorbed dose was derived from unbound mAbs freely circulating in the abdominal cavity, also using the Monte Carlo software. RESULTS: In the control groups given unlabeled MX35 or PBS, all 18 animals had ascites, 6 of 9 animals in each group had macroscopic tumors, and all animals had microscopic growth. In the 3 groups given different amounts of (211)At-MX35, only 3 of 25 animals developed ascites. None of these animals had any sign of macroscopic tumors, but 8 had microscopic growth. In the group given (211)At-MOv18, no animals had ascites or macroscopic tumors, but 3 of 10 animals had microscopic tumors. After injecting 400 kBq of (211)At-MX35, the absorbed dose due to specific binding, for a cell cluster with a radius of 50 microm, ranged from 413 to 223 Gy between 0- and 45-microm distance from the cluster center, assuming a homogeneous distribution of (211)At-MX35 in the cluster. The contribution from unbound (211)At-MX35 and (211)At-MX35 only distributed on the cluster surface, for this cluster size, ranged from 7 to 14 Gy and from 29 to 94 Gy, between 0- and 45-microm distance from the cluster center, respectively. The calculated total absorbed doses are in a clinically relevant range and were effective as verified in the nude mice with subclinical intraperitoneal growth of OVCAR-3 cells. CONCLUSION: (211)At-MX35 injected intraperitoneally exhibits a high efficacy when treating micrometastatic growth of the ovarian cancer cell line OVCAR-3 on the peritoneum of nude mice.
|
|
| 6. |
|
|
| 7. |
- Ostwald, Madelene, 1966-, et al.
(author)
-
Biomass potential on Indian wasteland
- 2008
-
In: Forest Adaptation 2008, IUFRO, SLU and FAO,2008. - Umeå : FAO/SLU.
-
Conference paper (peer-reviewed)
|
|
| 8. |
|
|
| 9. |
- Palm, Matilda, 1979, et al.
(author)
-
Application of Clean Development Mechanism to forest plantation projects and rural development in India
- 2009
-
In: Applied Geography. - : Elsevier BV. - 0143-6228 .- 1873-7730. ; 29:1, s. 2-11
-
Journal article (peer-reviewed)abstract
- This paper analyses the prospects for establishing afforestation and reforestation Clean Development Mechanism (CDM) projects in Karnataka State, India. Building on multi-disciplinary fieldwork, the aim is to: (i) establish what type of plantations and forests that would best suit a forest-based project activity, considering global climate benefits and local sustainable development objectives; (ii) identify the parameters that are important for ensuring sustainable development at the local level and (iii) develop a transparent ranking tool for the assessment of possible forest-based project activities. Using equal weights for the ranking parameters and a 30-year time horizon, the ranking shows that plantations managed with the shortest rotation period (5 years) would be most suitable for forest-based project activities. However, the performance of individual forest-based project activities will depend on local conditions, which need to be reflected in the weighting procedure. Sensitivity analysis shows that when weights are varied, other forest types can become the preferred option. Based on a combination of the sensitivity analysis and results from the fieldwork, it can be concluded that successful implementation of forest-based project activities will require local participation and are likely to involve multiple forest products and environmental services demanded by the local community.
|
|
| 10. |
- Palm, S, et al.
(author)
-
Panmixia in European eel revisited : no genetic difference between maturing adults from southern and northern Europe
- 2009
-
In: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 103:1, s. 82-89
-
Journal article (peer-reviewed)abstract
- Previous studies of genetic structure in the European eel have resulted in seemingly conflicting results, ranging from no detectable heterogeneity to small but statistically significant differences and isolation by distance patterns among eels sampled across the continental range. Differences with respect to sampling design and choice of molecular markers, combined with a lack of power estimates, complicate comparisons of existing results. In this study we have used six microsatellite markers and, for the first time, compared maturing silver eels of known age from southern and northern Europe (Italy and Baltic Sea). In comparison with previous studies, our data may give a better representation of potential spawning stocks because eels were sampled when having begun their migration toward the presumed spawning area in the Sargasso Sea. Despite large sample sizes (404 and 806 individuals) we could not observe any signs of genetic differentiation (average F-ST = -0.00003, P = 0.61), and a power analysis showed that the true level of heterogeneity (if existing) must be exceedingly small to have remained undetected (say, F-ST <0.0004). A tendency for slightly increased genetic differences between cohorts over time could be seen, but the amount of temporal change was minor and not statistically significant. Our findings reiterate the notion that previous reports of continental genetic differentiation in the European eel may be largely explained by uncontrolled temporal variation between juvenile glass eel samples. Heredity (2009) 103, 82-89; doi: 10.1038/hdy.2009.51; published online 6 May 2009
|
|
