| 1. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of (125)I- and (111)in-labeled epidermal growth factor(EGF) bound to cultured A431 tumor cells
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 827-35
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Tidskriftsartikel (refereegranskat)abstract
- Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.
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| 2. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of 125I- and 111in-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 827-835
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.
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| 3. |
- Orlova, Anna, et al.
(författare)
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Cellular processing of indirectly astatinated and iodinated mAb A33 in SW1222 cultured cells
- 2001
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 44:suppl 1, s. S715-S717
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- In principle, alpha-emitting radionuclides, such as 211At, are more efficient than beta-emitters to inactive single disseminated cancer cells. However, cellular processing of astatinated proteins has not yet been studied in detail. In this study an anti-colorectal cancer monoclonal antibody (mAb) A33 was indirectly labeled with 211At and for comparison with 125I. Binding and retention of radioactivity was studied in the colorectal cancer cell-line SW1222. A similar pattern of binding and retention of the two radiohalogens was seen. The main difference found, that the retention time of astatinated mAb in SW1222 was almost two times longer, might be of advantage in radionuclide therapy.
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| 4. |
- Orlova, Anna, et al.
(författare)
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Targeting against epidermal growth factor receptors : Cellular processing of astatinated EGF after binding to cultured carcinoma cells
- 2004
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 24:6, s. 4035-4042
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available.MATERIALS AND METHODS:We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF.RESULTS: The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF.CONCLUSION:The long retention of astatine might be advantageous for radionuclide therapy.
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| 5. |
- Ahlgren, Ewa, 1959-, et al.
(författare)
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Neurocognitive impairment and driving performance after coronary artery bypass surgery
- 2003
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 23:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neurocognitive impairment is common after cardiac surgery but few studies have examined the relationship between postoperative neuropsychological test performance and everyday behavior. The influence of postoperative cognitive impairment on car driving has previously not been investigated. The purpose of this study was to evaluate neurocognitive function and driving performance after coronary artery bypass grafting (CABG).Methods: Twenty-seven patients who underwent coronary artery bypass grafting with standard cardiopulmonary bypass technique and 20 patients scheduled for percutaneous coronary intervention (PCI) under local anesthesia (control group) were enrolled in this prospective study conducted from April 1999 to September 2000. Complete data were obtained in 23 and 19 patients, respectively. The patients underwent neuropsychological examination with a test battery including 12 tests, a standardized on-road driving test and a test in an advanced driving simulator before and 4–6 weeks after intervention.Results: More patients in the coronary artery bypass grafting group (n=11, 48%) than in the percutaneous coronary intervention group (n=2, 10%) showed a cognitive decline after intervention (P=0.01). In the on-road driving test, patients who underwent coronary artery bypass grafting deteriorated after surgery in the cognitive demanding parts like traffic behavior (P=0.01) and attention (P=0.04). Patients who underwent percutaneous intervention deteriorated in maneuvering of the vehicle (P=0.04). No deterioration was detected in the simulator in any of the groups after intervention. Patients with a cognitive decline after intervention also tended to drop in the on-road driving scores to a larger extent than did patients without a cognitive decline.Conclusion: This study indicates that cognitive functions important for safe driving may be influenced after cardiac surgery.
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| 6. |
- Brismar, Anna, 1971-
(författare)
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Environmental considerations in the planning of large dam projects : a study on Environmental Impact Statements and the Southeastern Anatolia Project
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Large dam projects have played a key role in supporting societal development in the past and continue to be launched, primarily in developing countries. However, large dam projects also cause extensive environmental impacts in the river system, which may reduce the river system's capacity to provide goods, services, and other values apart from those generated by the project. The Environmental Impact Statement (ElS) has become a key instrument for enabling prevention, minimization, and mitigation of significant adverse environmental effects of major projects in early planning. The potential of EISs to support compromise building between conflicting interests is also increasingly recognized. In reality, the great potentials of the ElS are rarely fully utilized, which motivate further improvements.This thesis has three main objectives, Le. (i) to examine the motives behind large dam projects, their impact on project planning, and some constraints for full project realization, (ii) to identify shortcomings in EISs and other project-related reports regarding the extent to and manner in which potential environmental effects of large dam projects are attended to, and (iii) to suggest measures for how to improve the capacity of EISs to support impact minimization and compromise building in project plarming and decision-making.Based on a case study on the Southeastern Anatolia Project (GAP) in southeast Turkey, it was found that the objectives and planning of large dam projects can change significantly over time, in response to changes in the underlying ambitions and motives for development. While changes to the design may increase the dam's technical capacity to store water and generate hydropower, the actual potential to utilize its installed capacities during recurrent droughts may be limited. An increased scale and number ofdam project objectives may also lead to increased competition over the river water. Full realization of dam project objectives may be hampered by the climate and by growing water demands of competing uses. Moreover, an analysis of GAP-related reports revealed imbalances in the total degree of attention given to individual environmental problems, different categories of environmental problems, and to environmental problems of dam projects and irrigation schemes, respectively, as weIl as shifts in the focus of attention over time from early plarming to implementation. The fmdings suggest that project-related reports tend to focus on problematic environmental conditions that motivate project implementation, and on potential environmental effects that may undermine project productivity, viability, or longevity, particularly in planning and early implementation. In contrast, those potential environmental effects with no apparent bearing on the financial or operational success of the project tend to be largely neglected unless strong incentives are created.The analysis ofEISs of large dam projects revealed shortcomings in the attention given to root causes and impact pathways involved in the generation of higher-order environmental effects and cumulative impacts. Important imbalances were also found in the degree of attention given to different types of environmental effects. In order to improve the capacity of EISs to explain how higher-order effects and cumulative impacts may arise, network analysis and cause-effect diagrams should be increasingly adopted. This thesis also proposes a conceptual framework to facilitate a comparison of desired and undesired effects, based on the view of a river system as a provider of goods and services, which enables the translation of ecological effects into their societal and economic implications.
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| 7. |
- Dolby, Viveka, et al.
(författare)
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Overexpression and functional characterisation of the human melanocortin 4 receptor in Sf9 cells
- 2004
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 37:2, s. 455-461
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Tidskriftsartikel (refereegranskat)abstract
- The human melanocortin 4 receptor (MC4r) was successfully expressed in Sf9 cells using the baculovirus infection system. N- and C-terminally His-tagged receptors generated B-max values of 14 and 23 pmol receptor/mg membrane protein, respectively. The highest expression level obtained with the C-terminally His-tagged MC4r corresponded to 0.25 mg active receptor/litre culture volume. Addition of a viral signal peptide at the N-terminus of the His-tagged MC4r did not improve the expression level. Confocal laser microscopy studies revealed that both the N- and C-terminally tagged MC4r did not accumulate intracellularly and were mainly located in the plasma membrane. The recombinant receptors showed similar affinity for the agonist NDP-MSH (K-d = 11 nM) as to MC4r expressed in mammalian cells. Functional coupling of the highest expressed C-terminal tagged receptor to endogenous Galpha protein was demonstrated through 6TPgammaS binding upon agonist stimulation of the receptor. K-i values for the ligands MTII, HS014, alpha-, beta-, and gamma-MSH are comparable to the values obtained for MC4r expressed in mammalian cells. (C) 2004 Elsevier Inc. All rights reserved.
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| 8. |
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| 9. |
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| 10. |
- Höglund, Johanna, et al.
(författare)
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Optimized indirect (76)Br-bromination of antibodies using N-succinimidyl para-[76Br]bromobenzoate for radioimmuno PET
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 837-43
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibody 38S1 was radiobrominated with the positron emitter (76)Br (T(1/2) = 16.2 h). Indirect labeling was performed using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB) as the precursor molecule. SPMB was labeled using Chloramine-T yielding N-succinimidyl para-[(76)Br]bromobenzoate, which was then conjugated to the antibody. Optimization of the labeling conditions and further conjugation gave a total yield ( mean+/-max error) of 49+/-2%. The immunoreactivity of the antibodies was retained after labeling. Thus, antibodies intended for positron emission tomography can be labeled with (76)Br, which gives high yields and preserved immunoreactivity when using the SPMB technique described.
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| 11. |
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| 12. |
- Jacobs, Anna, Ph. D., et al.
(författare)
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Characterization of water-soluble hemicelluloses from spruce and aspen employing SEC/MALDI mass spectroscopy
- 2002
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Ingår i: Carbohydrate Research. - 1873-426X .- 0008-6215. ; 337:8, s. 711-717
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Tidskriftsartikel (refereegranskat)abstract
- Partly depolymerized hemicelluloses isolated from wood chips of spruce and aspen employing microwave treatment were resolved using size-exclusion chromatography (SEC) into oligo- and polysaccharide fractions containing components with a narrow range of sizes, as determined by MALDI mass spectroscopy. The degree of substitution with acetyl moieties (DS) was also calculated on the basis of the MALDI-MS spectra obtained prior to and following deacetylation. For spruce hemicelluloses, the low molecular mass fraction contained small arabino-4-O-methylglucuronoxylan oligosaccharides, with DP values ranging from 4 to ~20, separated primarily on the basis of their charge density. The fraction eluted last consisted of an O-acetyl-(galacto)glucomannan polysaccharide of peak-average DP value (DPp) 14. The degree of substitution with acetyl groups (DS) decreased with decreasing DP, a value DS of 0.39 being obtained for the fraction with DPp 12. For the aspen hemicelluloses, the SEC fractions eluted first contained an acidic O-acetyl-4-O-methylglucuronoxylan polysaccharide with DP ranging from 10 to ~28 and an average DS of ~0.75. The fractions eluted last consisted of oligosaccharide mixtures composed primarily of small neutral O-acetyl-xylooligosaccharides (DPp 6, DS 0.41), together with minor quantities of an O-acetyl-glucomannan.
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| 13. |
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| 14. |
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| 15. |
- Lundqvist, Anette, et al.
(författare)
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8 av 10 barnmorskor gav information om folsyra : de flesta ansåg sig ha otillräckliga kunskaper
- 2004
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 101:15-16, s. 1380-1386
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Deficiency of folic acid increases the risk for neural tube defects among newborn children and megaloblastic anaemia in the mother. The aim of this study was to make a survey of how midwives working in maternity health care, family planning guidance, and specialist prenatal care in a Swedish county inform women of childbearing age about folic acid. The questionnaire study showed that 79% of the midwives informed the women about folic acid. Usually, the women received information first when they asked for it and midwifes were less prone to inform young women about folic acid. 87% of the midwives felt that they did not know enough about folic acid. Conclusions: Midwives play an important role in information about the need of folic acid intake for women in childbearing age. Changes in local routines, guidelines and further education of midwifes would subsequently provide information about the importance of folic acid to women in childbearing age.
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| 16. |
- Lundqvist, Anita, et al.
(författare)
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Both empowered and powerless: mothers' experiences of professional care when their newborn dies.
- 2002
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Ingår i: Birth. - 0730-7659. ; 29:3, s. 192-199
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Tidskriftsartikel (refereegranskat)abstract
- The death of a newborn is a complex and tragic situation, the uncertain and stressful nature of which places emotional burdens on the parents. The aim of this study was to examine and illuminate mothers' experiences and perceptions of the care given to them at neonatal clinics while facing the threat and the reality of losing their baby. METHOD: Interviews were performed, in the form of conversations, with 16 mothers approximately 2 years after the death of their newborns. The interviews were analyzed using a hermeneutic phenomenological method. RESULTS: The primary themes identified were feeling empowered and feeling powerless. Three related themes to feeling empowered were a sense of nearness-supporting confidence; a sense of encouragement-supporting self-esteem; and a sense of empathy-supporting comfort. Three related themes to feeling powerless were a sense of distance-leading to strength or adjustment; a sense of violation-leading to helplessness and despondency; and a sense of disconnection-leading to insecurity and discouragement. All mothers felt both empowered and powerless. When experiencing empowering care, they had a feeling of encountering benevolence, with respect to their individual desires. Experiencing competent care without humane treatment madethemfeel powerless, and they were neither respected as a mother nor a person. CONCLUSIONS: Feelings of empowerment emerged when the health care professionals not only saw the mother as an individual but also "saw through the mothers' eyes" and "felt with the mother's feelings".Feelings of powerlessness emerged when the similarity in the lifeworld (i.e., the world of lived experiences) differed, and the perspectives of the mothers and the health care professionals did not correspond. (BIRTH 29:3 September 2002)
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| 17. |
- Lundqvist, Anna, 1944-
(författare)
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Cognitive functions in drivers with brain injury : Anticipation and adaption
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to improve the understanding of what cognitive functions are important for driving performance, investigate the impact of impaired cognitive functions on drivers with brain injury, and study adaptation strategies relevant for driving performance after brain injury. Finally, the predictive value of a neuropsychological test battery was evaluated for driving performance.Main results can be summarized in the following conclusions: (a) Cognitive functions in terms of attentional and dynamic working memory-related functions are relevant for driving performance. (b) Neuropsychological impairments in information processing speed, divided and focused attention, requiring working memory, are associated to limitations in driving performance. In addition, qualitative aspects of driving problems especially impaired anticipatory attention appeared to constrain driving performance. (c) A neuropsychological test battery assessing speed of information processing and attention in terms of working memory predicted driving performance. In addition, cognitive factors are relevant for interpretation of driving problems qualitatively. (d) Driving speed adjustment and anticipatory attention were adaptive strategies for driving after brain injury. Interest in driving, motivation for driving safely, and driving experience appeared also relevant for driving after brain injury. (e) Collaboration between medical, neuropsychological and driving expertise is recommended for a total evaluation of driving performance after brain injury.Anticipatory attention was considered a working memory based attentional system, directing the processing resources flexibly and appropriately between the different information processing components. Thus, anticipatory attention demonstrated qualitatively that working memory is a prominent function in a real driving context.
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| 18. |
- Lundqvist, Anna, et al.
(författare)
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Driving problems and adaptive driving behavior after brain injury : A Qualitative Assessment
- 2001
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Ingår i: Neuropsychological Rehabilitation. - : Informa UK Limited. - 0960-2011 .- 1464-0694. ; 11:2, s. 171-185
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Tidskriftsartikel (refereegranskat)abstract
- One professional driving expert was interviewed after each of 22 on-road driving occasions with brain-injured patients. Driving problems were found in five prescribed qualitative dimensions: speed, manoeuvring, position, attention, and traffic behaviour. In addition, three non-prescribed qualitative dimensions were found: orientation, decision-making, and confidence. Also, adaptive aspects important for safe driving despite brain injury were identified: anticipatory attention, slowing down speed, interest and motivation for safe driving, and driving experience. The results are discussed in terms of a hierarchical model of driving performance. In addition, driving problems and adaptive aspects are discussed in relation to attention and information processing. Anticipatory attention is considered a working memory-based attention system, which is essential for driving quality. Practical implications are outlined, for example, educational practice for driving evaluators and adaptive driving behaviour for patients facilitating driving practice as a part of the rehabilitation programme.
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| 19. |
- Lundqvist, Anita, et al.
(författare)
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Experiencing neonatal death: an ambivalent transition into motherhood
- 2002
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Ingår i: Pediatric nursing. - 0097-9805. ; 28:6, s. 621-625
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To illuminate the lived experience of women facing the threat of lossing their newborn child and then experiencing the reality of their infant's death. STUDY DESIGN: Sixteen women were interviewed approximately 2 years after the death of their infant using a hermeneutic phenomenological approach. FINDINGS: The main theme was ambivalent transition into motherhood. The women went through the whole life-span of their infant during a very short time. The women's narratives were interpreted as broken expectations, total confusion, reality awareness, consciously leave-taking, and elusive grief. CONCLUSIONS: Women need the opportunity to evolve their own patterns and rhythms in the ambivalent transition from expected motherhood to experiencing neonatal dying and death. Knowledge about the individuality of this process may assist nurses in improving the quality of care.
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| 20. |
- Lundqvist, Anita, et al.
(författare)
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Neonatal end-of-life care in Sweden.
- 2003
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Ingår i: Nursing in critical care. - : Wiley. - 1478-5153 .- 1362-1017. ; 8:5, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- A survey was carried out of Swedish neonatal end-of-life regarding practice before birth, at birth, during dying and after death using a descriptive questionnaire with close-ended questions and individual comments The practice in 32 of 38 neonatal units, as described by the head nurse or the registered nurses, was largely similar. Respectful treatment of both the neonate and the parents during neonatal end-of-life care was indicated Differences were found in pre-natal care concerning the information about the risks of pre-term birth, the opportunity for parents to view a pre-term neonate and meet its family, as well as a social worker Practice directly after birth was also different. A little less than half of the units answered that they gave a description of the seriously ill neonate to the parents before the first visit to the ward Practice during dying indicated that only a few units permitted the neonate to die at home
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| 21. |
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| 22. |
- Lundqvist, Anna, et al.
(författare)
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Neuropsychological aspects of driving after a stroke : in the simulator and on the road
- 2000
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Ingår i: Applied Cognitive Psychology. - 0888-4080. ; 14:2, s. 135-150
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Tidskriftsartikel (refereegranskat)abstract
- Thirty patients with stroke and 30 matched controls participated in the study (mean age 68 years, mean interval since stroke onset 8.6 months). The patients performed significantly worse on cognitive and attentional processing measured by a neuropsychological test battery. The patients had significantly greater difficulty in allocating processing resources to a secondary information processing task during driving in an advanced simulator. The patients performed worse driving in real traffic, and had less driving skill; fifty per cent did not pass the driving test. The neuropsychological test battery showed a pattern with three factors: (1) attentional processing (2) executive capacity, and (3) cognitive processing. Regression models based on simulator driving variables and neuropsychological test variables respectively, overall classified correctly in 85% and 83% of the cases with respect to driving skill. Decreased cognitive and attentional processing were suggested to be associated with an overall speed impairment.
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| 23. |
- Lundqvist, Anna
(författare)
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Neuropsychological aspects of driving characteristics
- 2001
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Ingår i: Brain Injury. - 0269-9052. ; 15:11, s. 981-984
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Tidskriftsartikel (refereegranskat)abstract
- Brain injury often causes impairments of cognitive functions, which may affect driving performance. The question of whether the brain-injured patient can resume car driving or not generally comes up during rehabilitation. The medical clinical examination, covering neurological status, screening of cognitive functions, and affective state, is insufficient in assessing relevant functions required for driving performance. A neuropsychological assessment and a driving test are additional parts of the driving assessment besides the medical examination. In this paper, neuropsychological test results and driving test results from four patients with brain injury are presented. The paper demonstrates the complementary value of neuropsychological assessment and a driving test: the relevance of cognitive factors for interpretation of driving problems, but also the relevance of a driving test to show compensatory capacity in some drivers with brain injury. Thus, collaboration between medical, neuropsychological and driving expertise can promote and deepen the total assessment of driving performance after brain injury.
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| 24. |
- Lundqvist, Jon, et al.
(författare)
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Characterization of galactoglucomannan extracted from spruce (Picea abies) by heat-fractionation at different conditions
- 2003
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Ingår i: Carbohydrate Polymers. - 0144-8617 .- 1879-1344. ; 51:2, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- Water-soluble hemicelluloses were extracted from spruce chips by microwave heat-fractionation. The galactoglucomannan (GGM) extraction was evaluated on the basis of weight-average molecular weight (MW), yield and carbohydrate composition of the GGM. The MW was determined by size-exclusion chromatography with column calibration using off-line MALDI-MS analysis, and determination of mannan content in the fractions collected. Water impregnated spruce chips were heat-fractionated at three different temperatures (180, 190, and 200oC). The spruce chips were also impregnated in NaOH solutions of different concentrations, and then heat-fractionated at 190oC for 5min. The highest mannan yield (78% based on the amount in the raw material) was obtained from water impregnated spruce chips heat-fractionated at 190oC for 5min (MW of 3800). The highest MW (14,000) was obtained from impregnation with 2% NaOH (190oC, 5min), but the yield of mannan was very low (3%). Impregnation with 0.025% NaOH and heat-fractionation at 190oC for 5min resulted in extraction of GGM with MW of 9500 and a mannan yield of 31%. When the spruce chips were impregnated with =<0.05% NaOH an O-acetyl-galactoglucomannan was extracted, whereas when higher NaOH charges were used in the impregnation, the extracted GGM lacked acetyl groups.
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| 25. |
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| 26. |
- Orlova, Anna, et al.
(författare)
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Closo-dodecaborate(2-)anion as a potential prosthetic group for attachment of astatine to proteins : Aspects of the labelling chemistry with Chloramine -T
- 2000
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - 0362-4803. ; 43:3, s. 251-260
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Closo-dodecarborate (2-) was proposed as a prosthetic group for direct labelling of proteins with 211At for radionuclide therapy. Astatination of closo-dodecarborate (2-) anion using Chloramine-T was studied, and the influence of pH, reaction time, amount of substrate and oxidant was determined. A maximum labelling yield of 55-75% was found in the pH range 7-8. A spontaneous astatination of closo-dodecarborate (2-) in the absence of Chloramine-T was also found, presumably due to generation of oxidising products from water radiolysis. Our results indicate that derivatives of closo-dodecarborate (2-) anion may be used as prosthetic groups for direct labelling of proteins.
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| 27. |
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| 28. |
- Orlova, Anna, et al.
(författare)
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Comparative biodistribution of the radiohalogenated (Br, I and At) antibody A33 : Implications for in vivo dosimetry
- 2002
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 17:4, s. 385-96
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Tidskriftsartikel (refereegranskat)abstract
- The alpha-emitter astatine-211 (T(1/2) = 7.2 h) has great potential for use in targeted radionuclide therapy. Its potent alpha-radiation makes (211)At unsuitable for dose planning. Its x-rays can be used for gamma-camera monitoring of the radioactivity distribution during therapy but not for accurate estimation of absorbed dose in critical organs. This study was intended to establish whether the absorbed dose delivered by astatinated antibody could be accurately determined by analogue labeling with radiohalogens, better suited for quantitative measurements in vivo. PET facilitates quantitative pharmacokinetics; possible halogen labels are, e.g., (76)Br (T(1/2) = 16.2 h) and (124)I (T(1/2) = 4.18 d). Antibody A33 was labeled with (76)Br, (125)I and (211)At using N-succinimidyl-p-halobenzoates. The conjugates were co-injected into Sprague-Dawley rats. Radioactivity concentrations in different organs and tissues were measured at three time points. Pharmacokinetic data were used to calculate absorbed doses. (125)I and (76)Br reflected the biokinetics of astatine reasonably well. The absorbed doses in bladder, kidney, pancreas, liver, bone and brain were determined with 10% accuracy. The absorbed doses in stomach, spleen and thyroid were underestimated by a factor 2-3. Positron-emitting analogues can be used to predict the astatine-derived dose in critical organs. Correction factors should be used for stomach, spleen and thyroid.
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| 29. |
- Orlova, Anna
(författare)
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Indirect Radiohalogenation of Targeting Proteins : Labelling Chemistry and Biological Characterisation
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In about half of all newly diagnosed cancer cases, conventional treatment is not adequately curative, mainly due to the failure of conventional techniques to find and kill residual cells and metastases, which might consist of only a few malignant cells, without causing unacceptable complications to healthy tissue. To solve the problem a more selective delivery of cytotoxic substances to tumour cells is needed. The approach applied here is called ‘tumour targeting’ and implies the use of biomolecules that recognise specific molecular structures on the malignant cell surface. Such molecules are then used for a selective transport of toxic agents to the cancer cells. The use of radionuclides as cytotoxic substances has a number of advantages: 1) radiation does not cause severe resistance; 2) there is a cross-fire effect and 3) smaller amounts of nuclides are required than other cytotoxic substances to cause the same damage. Such an approach is called radionuclide tumour therapy. Several factors are important for the success of radionuclide therapy, such as the pharmacokinetics of the radiolabelled substance and its radiocatabolites, as well as the physical and chemical properties of the radiolabel used.Nuclear properties of the label should be consistent with the problem to be solved: primary diagnostics; quantification of pharmacokinetics and dose planning; or therapy. From this point of view, radiohalogens are an attractive group of radiolabels. Halogens have nuclides with a variety of physical properties while the chemical and biological properties of halogens are very similar. The same labelling procedures can be used for all heavy halogens, i.e. bromine, iodine and astatine. It has been demonstrated that the biodistribution of proteins labelled with different heavy halogens is quite similar. The main goal of the study was to develop protein radiohalogenation methods that provide a stable halogen-protein bond, convenient labelling chemistry that preserves the binding properties of proteins, long intracellular retention of radioactivity in targeted cells and quick release of radiohalogenated catabolites from the blood circulation. Radiohalogenation of proteins using indirect methods was studied, including optimisation of labelling chemistry and biological characterisation of some labelled conjugates. Two groups for indirect radiohalogenation were used, representing two different labelling principles: activated ester of benzoic acid (1) and the derivative of closo-dodecaborate anion (2). The non-phenolic linker (1) as well as the borate-halogen moiety (2) probably prevent dehalogenation. The negative charge of the potential catabolic products of (2) might trap radiohalogens intracellularly.
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| 34. |
- Sundberg, Åsa Liljegren, et al.
(författare)
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[111In]Bz-DTPA-hEGF : Preparation and in vitro characterization of a potential anti-glioblastoma targeting agent
- 2003
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 18:4, s. 643-54
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Tidskriftsartikel (refereegranskat)abstract
- The overexpression of epidermal growth factor receptors, EGFR, in glioblastomas is well documented. Hence, the EGFR can be used as target structure for a specific targeting of glioblastomas. Both radiolabeled anti-EGFR antibodies and the natural ligand EGF are candidate agents for targeting. However, EGF, which has a rather low molecular weight (6 kDa), might have better tissue penetration properties through both normal tissue and tumors in comparison with anti-EGF antibodies and their fragments. The aim of this study was to prepare and evaluate in vitro an EGF-based antiglioma conjugate with residualizing label. Human recombinant EGF (hEGF) was coupled to isothiocyanate-benzyl-DTPA. The conjugate was purified from unreacted chelator using solid-phase extraction and labeled with (111)In. The labeling yield was 87% +/- 7%. The label was reasonably stable; the transchelation of (111)In to serum proteins was about 5% after incubation at 37 degrees C during 24 hours. The obtained [(111)In]benzyl-DTPA-hEGF conjugate was characterized in vitro using the EGFR expressing glioma cell line U343MGaCl2:6. The binding affinity, internalization, and retention of the conjugate were studied. The conjugate had receptor specific binding and the radioactivity was quickly internalized. The intracellular retention of radioactivity after interrupted incubation with conjugate was 71% +/- 1% and 59% +/- 1.5% at 24 and 45 hours, respectively. The dissociation constant was estimated to 2.0 nM. The results indicate that [(111)In]benzyl-DTPA-hEGF is a potential candidate for targeting glioblastoma cells, possibly using locoregional injection.
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| 35. |
- Swain, Ashok, et al.
(författare)
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Water & Development
- 2000
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Tolmachev, Vladimir, et al.
(författare)
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Approaches to improve cellular retention of radiohalogen labels delivered by internalising tumour-targeting proteins and peptides
- 2003
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Ingår i: Current Medicinal Chemistry. - 0929-8673 .- 1875-533X. ; 10:22, s. 2447-60
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Tidskriftsartikel (refereegranskat)abstract
- Specific targeting of radionuclides is a promising approach to improve diagnosis and treatment of tumors. Targeting vectors may be monoclonal antibodies directed toward tumour-specific antigens or regulatory peptides binding to receptors overexpressed on or by malignant cells. Depending on the aim of the procedure and the biokinetics of the targeting vectors, radionuclides with different nuclear properties (decay scheme, half-life, etc.) must be applied. Halogen radioisotopes are attractive since they exhibit a variety of nuclear properties suitable for various applications. At the same time, their chemistry shows great similarities, which enables the use of similar labelling procedures for different nuclides. A problem in using radiohalogens for labelling of tumour-targeting proteins and peptides is that the commonly used radiohalogenation methods provide labels, which, after internalisation and lysosomal digestion, rapidly "leak" from malignant cells as radiohalogenated degradation products. The main reason for such leakage is free diffusion of the radiometabolites through lysosomal and cellular membranes. This review describes current approaches in molecular design to improve cellular retention of radiohalogen labels. These approaches include the use of prosthetic groups for the attachment of radiohalogens to targeting vectors of bulky hydrophilic non-charged molecules, molecules positively charged at lysosomal pH and negatively charged molecules. The emphasis in this paper is on labelling chemistry and the results of the biological testing of labelled compounds.
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