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- Altai, Mohamed, et al.
(författare)
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Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting : Development of an optimized conjugation protocol and 177Lu labeling
- 2017
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Ingår i: Nuclear Medicine and Biology. - : Elsevier. - 0969-8051 .- 1872-9614. ; 54, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA–PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide 177Lu. We also studied the biodistribution profile of 177Lu-HP2 in mice, and evaluated pretargeting with 177Lu-HP2 in vitro and in vivo. Methods The biodistribution profile of 177Lu-HP2 was evaluated in NMRI mice and compared to the previously studied 111In-HP2. Pretargeting using 177Lu-HP2 was studied in vitro using the HER2-expressing cell lines BT‐474 and SKOV-3, and in vivo in mice bearing SKOV-3 xenografts. Results and conclusion Using an optimized production protocol for ZHER2:342-SR-HP1 the ligation time was reduced from 15 h to 30 min, and the yield increased from 45% to 70%. 177Lu-labeled HP2 binds specifically in vitro to BT474 and SKOV-3 cells pre-treated with ZHER2:342-SR-HP1. 177Lu-HP2 was shown to have a more rapid blood clearance compared to 111In-HP2 in NMRI mice, and the measured radioactivity in blood was 0.22 ± 0.1 and 0.68 ± 0.07%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i. In contrast, no significant difference in kidney uptake was observed (4.47 ± 1.17 and 3.94 ± 0.58%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i.). Co-injection with either Gelofusine or lysine significantly reduced the kidney uptake for 177Lu-HP2 (1.0 ± 0.1 and 1.6 ± 0.2, respectively, vs. 2.97 ± 0.87%ID/g in controls at 4 h p.i.). 177Lu-HP2 accumulated in SKOV-3 xenografts in BALB/C nu/nu mice when administered after injection of ZHER2:342-SR-HP1. Without pre-injection of ZHER2:342-SR-HP1, the uptake of 177Lu-HP2 was about 90-fold lower in tumor (0.23 ± 0.08 vs. 20.7 ± 3.5%ID/g). The tumor-to-kidney radioactivity accumulation ratio was almost 5-fold higher in the group of mice pre-injected with ZHER2:342-SR-HP1. In conclusion, 177Lu-HP2 was shown to be a promising secondary agent for affibody-mediated tumor pretargeting in vivo.
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- Halava, Heli, et al.
(författare)
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Influence of Retirement on Adherence to Statins in the Insurance Medicine All-Sweden Total Population Data Base
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Retirement has been suggested to reduce medication adherence, but no evidence is available for statins. We investigated changes in adherence to statins among Swedish adults after retirement. Methods A prospective cohort study was carried out on all individuals living in Sweden on 31 December 2004, alive in 2010, having purchased statins in the second half of 2005, and retired in 2008 (n=11 718). We used prescription dispensing data in 2006-2010 to determine nonadherence (defined as <80% of days covered by filled prescriptions) before and after old-age or disability retirement. Using multiple repeat measurements of filled statin prescriptions, we calculated the annual prevalence rates of nonadherence for those who continued therapy. Discontinuation was defined as no statin dispensations during a calendar year. Results After adjustment for age at retirement, the prevalence ratio (PR) of nonadherence after retirement in comparison with those before retirement was 1.23 [95% confidence interval (CI) 1.17-1.29] for the men and 1.19 (95% CI 1.13-1.26) for the women. A post-retirement increase in nonadherence was consistently observed across the strata of age at retirement, marital status, education, income, type of retirement, and participants with and without cardiovascular disease, the largest increases being observed for statin use in secondary prevention (men: PR 1.38, 95% CI 1.26-1.54; women: PR 1.43, 1.18-1.72). For primary prevention, the corresponding prevalence ratios were 1.18 (95% CI 1.13. 1.25) and 1.18 (95% CI 1.11-1.24), respectively. Interpretation Retirement appears to be associated with increased nonadherence to statin therapy among Swedish men and women.
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- Halava, Heli, et al.
(författare)
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Influence of Retirement on Adherence to Statins in the Insurance Medicine All-Sweden Total Population Data Base
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Retirement has been suggested to reduce medication adherence, but no evidence is available for statins. We investigated changes in adherence to statins among Swedish adults after retirement.METHODS: A prospective cohort study was carried out on all individuals living in Sweden on 31 December 2004, alive in 2010, having purchased statins in the second half of 2005, and retired in 2008 (n=11 718). We used prescription dispensing data in 2006-2010 to determine nonadherence (defined as <80% of days covered by filled prescriptions) before and after old-age or disability retirement. Using multiple repeat measurements of filled statin prescriptions, we calculated the annual prevalence rates of nonadherence for those who continued therapy. Discontinuation was defined as no statin dispensations during a calendar year.RESULTS: After adjustment for age at retirement, the prevalence ratio (PR) of nonadherence after retirement in comparison with those before retirement was 1.23 [95% confidence interval (CI) 1.17-1.29] for the men and 1.19 (95% CI 1.13-1.26) for the women. A post-retirement increase in nonadherence was consistently observed across the strata of age at retirement, marital status, education, income, type of retirement, and participants with and without cardiovascular disease, the largest increases being observed for statin use in secondary prevention (men: PR 1.38, 95% CI 1.26-1.54; women: PR 1.43, 1.18-1.72). For primary prevention, the corresponding prevalence ratios were 1.18 (95% CI 1.13‒1.25) and 1.18 (95% CI 1.11-1.24), respectively.INTERPRETATION: Retirement appears to be associated with increased nonadherence to statin therapy among Swedish men and women.
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- Hansson, Kristina, 1956-, et al.
(författare)
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Berättelser av lärare som blev forskare
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 2010 infördes genom skollagen (SFS 2010:800) nya krav på lärare i skolan att utbildningen ska ”vila på vetenskaplig grund och beprövad erfarenhet”. Staten har initierat olika policys för att styra akademiseringen av läraryrket, exempelvis via karriärreform och forskarskolor för lärare samt via särskilda satsningar för att ta fram modeller för samverkan kring praktiknära forskning mellan skolhuvudman och lärosäte. Denna studie intresserar sig för forskares perspektiv på läraryrkets akademisering och hur forskaren utifrån sina erfarenheter som både lärare i skolan och forskare i akademin ser på praktiknära forskning. Studien genomförs i form av en livsberättelsestudie där sju forskare (tidigare lärare) intervjuas av yrkesverksamma lärare som intresserar sig för forskning och utveckling i skolan. De teoretiska utgångspunkterna är policy enactment, academic drift och narrativ. Preliminära analyser visar att forskarnas livsberättelser pendlar mellan att å ena sidan betrakta akademiseringen som ett individuellt projekt, å andra sidan som något som kan bidra till skolans och lärarutbildningens utveckling. Några forskares livsberättelser visar att de framförallt antagit en identitet som forskare medan andra forskares livsberättelser visar att de fortfarande efter många år inom akademin främst identifierar sig som lärare på tillfälligt besök i akademin och med en ständig längtan tillbaka till skolan. Att befinna sig i en samverkande praktik tillsammans med lärare har gjort att forskarna på ett mer aktivt försöker knyta an till tidigare erfarenheter som lärare. Förskjutningar mot fördjupat samverkande ansatser kan också skönjas i forskarnas berättelser.
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| 8. |
- Head, Jenny, et al.
(författare)
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Socioeconomic differences in healthy and disease-free life expectancy between ages 50 and 75 : a multi-cohort study
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 29:2, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are striking socioeconomic differences in life expectancy, but less is known about inequalities in healthy life expectancy and disease-free life expectancy. We estimated socioeconomic differences in health expectancies in four studies in England, Finland, France and Sweden. Methods: We estimated socioeconomic differences in health expectancies using data drawn from repeated waves of the four cohorts for two indicators: (i) self-rated health and (ii) chronic diseases (cardiovascular, cancer, respiratory and diabetes). Socioeconomic position was measured by occupational position. Multistate life table models were used to estimate healthy and chronic disease-free life expectancy from ages 50 to 75. Results: In all cohorts, we found inequalities in healthy life expectancy according to socioeconomic position. In England, both women and men in the higher positions could expect 82-83% of their life between ages 50 and 75 to be in good health compared to 68% for those in lower positions. The figures were 75% compared to 47-50% for Finland; 85-87% compared to 77-79% for France and 80-83% compared to 72-75% for Sweden. Those in higher occupational positions could expect more years in good health (2.1-6.8 years) and without chronic diseases (0.5-2.3 years) from ages 50 to 75. Conclusion: There are inequalities in healthy life expectancy between ages 50 and 75 according to occupational position. These results suggest that reducing socioeconomic inequalities would make an important contribution to extending healthy life expectancy and disease-free life expectancy.
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- Honarvar, Hadis, et al.
(författare)
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Evaluation of the first Sc-44-labeled Affibody molecule for imaging of HER2-expressing tumors
- 2017
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Ingår i: Nuclear Medicine and Biology. - : Elsevier. - 0969-8051 .- 1872-9614. ; 45, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Affibody molecules are small (58 amino acids) high-affinity proteins based on a tri-helix nonimmunoglobulin scaffold. A clinical study has demonstrated that PET imaging using Affibody molecules labeled with Ga-68 (T-1/2 = 68 min) can visualize metastases of breast cancer expressing human epidermal growth factor receptor type 2 (HER2) and provide discrimination between tumors with high and low expression level. This may help to identify breast cancer patients benefiting from HER2-targeting therapies. The best discrimination was at 4 h post injection. Due to longer half-life, a positron-emitting radionuclide Sc-44 (T-1/2 = 4.04 h) might be a preferable label for Affibody molecules for imaging at several hours after injection. Methods: A synthetic second-generation anti-HER2 Affibody molecule Z(HER2:2891) was labeled with Sc-44 via a DOTA-chelator conjugated to the N-terminal amino group. Binding specificity, affinity and cellular processing Sc-44-DOTA-Z(HER2:2891) and Ga-68-DOTA-Z(HER2:2891) were compared in vitro using HER2-expressing cells. Biodistribution and imaging properties of Sc-44-DOTA-Z(HER2,2891) and Ga-68-DOTA-Z(HER2:2891) were evaluated in Balb/c nude mice bearing HER2-expression xenografts. Results: The labeling yield of 98 +/- 2% and specific activity of 7.8 GBq/mu mol were obtained. The conjugate demonstrated specific binding to HER2-expressing SKOV3.ip cells in vitro and to SKOV3.ip xenografts in nude mice. The distribution of radioactivity at 3 h post injection was similar for Sc-44-DOTA-Z(HER2:2891) and Ga-68-DOTA-Z(HER2:2891), but the blood clearance of the Sc-44-labeled variant was slower and the tumor-to-blood ratio was reduced (15 +/- 2 for (SC)-S-44-DOTA-Z(HER2:2891) vs 46 +/- 9 for Ga-68-DOTA-Z(HER2.2891)). At 6 h after injection of Sc-44-DOTA-Z(HER2,2891) the tumor uptake was 8 +/- 2% IA/g and the tumor-to-blood ratio was 51 +/- 8. Imaging using small-animal PET/CT demonstrated that (SC)-S-44-DOTA-ZHER2,2891 provides specific and high-contrast imaging of HER2-expressing xenografts. Conclusion: The Sc-44- DOTA-Z(HER2:2891) Affibody molecule is a promising probe for imaging of HER2-expression in malignant tumors.
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