| 1. |
- Almqvist, Ylva, et al.
(författare)
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Biodistribution of At-211-Labeled humanized monoclonal antibody A33
- 2007
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:4, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.
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| 2. |
- Almqvist, Ylva, et al.
(författare)
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In vitro and in vivo characterization of 177Lu‑huA33 : A radioimmunoconjugate against colorectal cancer
- 2006
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 33:8, s. 991-998
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33. METHODS: huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. RESULTS: The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo. CONCLUSION: The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.
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| 3. |
- Almqvist, Ylva, et al.
(författare)
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In vitro characterization of 211 At-labeled antibody A33 : a potential therapeutic agent against metastatic colorectal carcinoma
- 2005
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 20:5, s. 514-523
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Tidskriftsartikel (refereegranskat)abstract
- The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
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| 4. |
- Almqvist, Ylva, 1974-
(författare)
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Targeted Therapy of Colorectal Cancer : Preclinical Evaluation of a Radiolabelled Antibody
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Targeted radiotherapy (TRT) of cancer is a promising approach that enables selective treatment of tumour cells, while sparing normal tissue. The humanized monoclonal antibody A33 (huA33) is a potential targeting agent for TRT of colorectal cancer, since its antigen is expressed in more than 95 % of all colorectal carcinomas. The aim of this thesis was to evaluate the therapeutic potential of the two huA33-based TRT-conjugates, 177Lu-huA33, and 211At-huA33. The conjugates 177Lu-huA33, and 211At-huA33, bound specifically to colorectal cancer cells, both in vitro and in vivo. A dose dependent cytotoxic effect of 211At-huA33 was also demonstrated in vitro. From a therapeutic perspective, both conjugates had a favourable biodistribution in tumour-bearing nude mice, with high tumour uptake and a low uptake in normal organs (with the exception of an expected thyroid uptake of 211At). After injection of 211At-huA33, the blood absorbed a slightly higher dose than the tumour, but for 177Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of 177Lu-huA33 in tumour-bearing mice, the tumours could be clearly visualised by gamma camera imaging, with very low interference from normal tissue radioactivity. In an experimental therapy study, also performed in tumour-bearing mice, there was an excellent therapeutic effect of 177Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of 177Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances. In conclusion, this thesis demonstrates that the therapeutic conjugates 177Lu-huA33, and 211At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.
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| 5. |
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| 6. |
- Babaei, Mohammad Hossein, et al.
(författare)
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[99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo : preparation and pre-clinical evaluation
- 2005
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 13:6, s. 1169-75
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Tidskriftsartikel (refereegranskat)abstract
- Expression of epidermal growth factor receptors (EGFR) has prognostic and predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo may give valuable diagnostic information. The epidermal growth factor (EGF), a natural ligand, is a possible candidate for the targeting of EGFR. The present study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine-3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells with nanomolar affinity, and demonstrated good intracellular retention. The complex with EDDA demonstrated much higher stability in blood serum and during cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR expression in vivo.
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| 7. |
- Benderix, Ylva, 1953-, et al.
(författare)
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Barn med neuropsykiatriskt funktionshinder
- 2009
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Ingår i: PEDIATRISK OMVÅRDNAD. - Stockholm : LIBER. - 9789147093274 ; , s. 309-315
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Ginsberg, Ylva, et al.
(författare)
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Maternal infection requiring hospitalization during pregnancy and attention-deficit hyperactivity disorder in offspring : a quasi-experimental family-based study
- 2019
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Ingår i: Journal of Child Psychology and Psychiatry. - : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 60:2, s. 160-168
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal infection during pregnancy (IDP) has been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. However, infection is associated with social adversity, poor living conditions and other background familial factors. As such, there is a need to rule out whether the observed association between maternal IDP and ADHD might be attributed to such confounding.METHODS: This nationwide population-based cohort study using a family-based, quasi-experimental design included 1,066,956 individuals born in Sweden between 1992 and 2002. Data on maternal IDP (bacterial or viral) requiring hospitalization and ADHD diagnosis in offspring were gathered from Swedish National Registers, with individuals followed up through the end of 2009. Ordinary and stratified Cox regression models were used for estimation of hazard ratios (HRs) and several measured covariates were considered. Cousin- and sibling-comparisons accounted for unmeasured genetic and environmental factors shared by cousins and siblings.RESULTS: In the entire population, maternal IDP was associated with ADHD in offspring (HR = 2.31, 95% CI = 2.04-2.61). This association was attenuated when accounting for measured covariates (HR = 1.86, 95% CI = 1.65-2.10). The association was further attenuated when adjusting for unmeasured factors shared between cousins (HR = 1.52, 95% CI = 1.12-2.07). Finally, the association was fully attenuated in sibling comparisons (HR = 1.03, 95% CI = 0.76-1.41).CONCLUSIONS: This study suggests that the association between maternal IDP and offspring ADHD is largely due to unmeasured familial confounding. Our results underscore the importance of adjusting for unobserved familial risk factors when exploring risk factors for ADHD.
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| 9. |
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| 10. |
- Niia, Anna
(författare)
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Participation in school for children in socially challenged areas : Achieving and socializing
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish school is not only an institution for learning. It is also the most significant social context for its students. In the Swedish regulatory documents for school the importance of democracy, democratic values and becoming a citizen of a democratic society is emphasized, as is the importance of interaction. When the number of students with foreign background is increasing in Swedish classrooms, there can be cultural and linguistic challenges to this. Getting students, as well as their parents, who might be newly arrived in Sweden or have lesser linguistic skills to participate in the school context demands to overcome language as well as cultural barriers.This research emanates from the notion of positive academic outcomes due to increasing participation in school. The studies focus on the relationships between teachers’ and students’ ratings of availability of school related activities and the frequency of attending them. Students’ and teachers’ ratings are subjected to principal component analysis showing different outcomes where teachers have an academic focus and students have a social focus. Teacher ratings of frequency of attending are related to academic achievement while student ratings are not.Parental involvement in terms of communication with school is also explored showing over all coherence between parents and teachers. Teachers rate the communication and trust between school and home higher regarding students with lower grades.Students with native and non-native mother tongue rate the availability and frequency of attending in school activities differently. Student with a non-native mother tongue rate the availability lower but their frequency of attending higher. Teachers’ ratings do not differ between students with native or non-native mother tongue.This thesis assesses participation in terms of attending but not involvement. A review of studies in the Nordic countries that study participation shows that attendance is often used as a measurement of participation but often rated by an observer. This research shows that the complexity of the concept of participation creates challenges in the pursuit of capturing it in scientific studies.The results show that students experience their school context differently than teachers, there are also differences between students with native and non-native mother tongue. Teachers have an academic focus while students have more of a social focus. This is especially pronounced for students with non-native mother tongue. As the number of students with foreign background is increasing, so is the number of students with non-native mother tongue. In order to promote participation in school for all students and to provide them with the prerequisites to become citizens of a democratic society, school needs to be more receptive to students own perception of the school context.
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| 11. |
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| 12. |
- Steffen, Ann-Charlott, et al.
(författare)
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Biodistribution of 211At labeled HER-2 binding affibody molecules in mice
- 2007
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 17:5, s. 1141-1147
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Tidskriftsartikel (refereegranskat)abstract
- The size of affibody molecules makes them suitable as targeting agents for targeted radiotherapy with the alpha-emitter 211At, since their biokinetic properties match the short physical half-live of 211At. In this study, the potential for this approach was investigated in vivo. Two different HER-2 binding affibody molecules were radiolabeled with 211At using both the linker PAB (N-succinimidyl-para-astatobenzoate) and a decaborate-based linker, and the biodistribution in tumor-bearing nude mice was investigated. The influence of L-lysine and Na-thiocyanate on the 211At uptake in normal tissues was also studied. Based on the biokinetic information obtained, the absorbed dose was calculated for different organs. Compared with a previous biodistribution with 125I, the 211At biodistribution using the PAB linker showed higher uptake in lungs, stomach, thyroid and salivary glands, indicating release of free 211At. When the decaborate-based linker was used, the uptake in those organs was decreased, but instead, high uptake in kidneys and liver was found. The uptake, when using the PAB linker, could be significantly reduced in some organs by the use of L-lysine and/or Na-thiocyanate. In conclusion, affibody molecules have suitable blood-kinetics for targeted radionuclide therapy with 211At. However, the labeling chemistry affects the distribution in normal organs to a high degree and needs to be improved to allow clinical use.
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| 13. |
- Sundberg, Åsa Liljegren, et al.
(författare)
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Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with 211At-EGF
- 2003
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 30:10, s. 1348-56
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Tidskriftsartikel (refereegranskat)abstract
- The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ['Iressa' (trademark of the AstraZeneca group of companies), ZD1839] increases the cellular uptake of radiolabelled epidermal growth factor (EGF). We investigated gefitinib treatment combined with astatine-211 EGF targeting in vitro using two cell lines expressing high levels of EGFR: A431 (sensitive to gefitinib) and U343MGaCl2:1 (resistant to gefitinib). In both cell lines, the uptake of 211At-EGF was markedly increased by concomitant treatment with gefitinib. Survival was investigated using both a clonogenic survival assay and a cell growth assay. Combined gefitinib and 211At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with 211At-EGF alone. In A431 cells, 211At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. These results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours and decrease the effect of such therapy in gefitinib-sensitive tumours.
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