| 1. |
- Altai, Mohamed, et al.
(author)
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Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA
- 2012
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In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 518-529
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Journal article (peer-reviewed)abstract
- Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.
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| 2. |
- Andersson, Magnus, et al.
(author)
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Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
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Reports (other academic/artistic)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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| 3. |
- Ivarsson, Anneli, et al.
(author)
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Prevalence of Childhood Celiac Disease and Changes in Infant Feeding
- 2013
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In: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 131:3, s. E687-E694
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Between 1984 and 1996, Sweden experienced an "epidemic" of clinical celiac disease in children andlt;2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohorts ascertained infant feeding. less thanbrgreater than less thanbrgreater thanMETHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios. less thanbrgreater than less thanbrgreater thanRESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60-0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding). less thanbrgreater than less thanbrgreater thanCONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable. Pediatrics 2013;131:e687-e694
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| 4. |
- Malmberg, Jennie, et al.
(author)
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Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts.
- 2012
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 481-492
-
Journal article (peer-reviewed)abstract
- PURPOSE: In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. METHODS: A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with (111)In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. RESULTS: The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1), respectively. A comparative study of (111)In-labelled DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. (111)In-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues. (111)In-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation. (111)In-DOTA-Z(HER2:S1) and (111)In-NODAGA-Z(HER2:S1) demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of (111)In-NODAGA-Z(HER2:S1), 5.6 ± 0.4%ID/g, was significantly lower than the uptake of (111)In-DOTA-Z(HER2:S1), 7.4 ± 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance. (111)In-NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. CONCLUSION: Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders (111)In-DOTA-Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer.
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| 5. |
- Malmberg, Jennie, et al.
(author)
-
Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with In-111 using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts
- 2012
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 481-492
-
Journal article (peer-reviewed)abstract
- Purpose In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. Methods A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with In-111, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. Results The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1), respectively. A comparative study of In-111-labelled DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. In-111-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues. In-111-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation. In-111-DOTA-Z(HER2:S1) and In-111-NODAGAZHER2: S1 demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of In-111-NODAGA-Z(HER2:S1), 5.6 +/- 0.4% ID/g, was significantly lower than the uptake of In-111-DOTA-Z(HER2:S1), 7.4 +/- 0.5% ID/g, presumably because of lower bioavailability due to more rapid clearance. In-111-NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. Conclusion Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders In-111-DOTA-Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer.
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| 6. |
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| 7. |
- Sandström, Olof, et al.
(author)
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Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in a sequential testing
- 2013
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 57:4, s. 472-476
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Journal article (peer-reviewed)abstract
- Objectives: The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening.Methods: Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted.Results: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies.Conclusions: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.
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| 8. |
- Tolmachev, Vladimir, et al.
(author)
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Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules
- 2011
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 22:5, s. 894-902
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Journal article (peer-reviewed)abstract
- Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of >95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) was 8.2 +/- 0.9% IA/g and the tumor-to-blood ratio was 31 +/- 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:239S) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.
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| 9. |
- Tolmachev, Vladimir, et al.
(author)
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Imaging of Insulinlike Growth Factor Type 1 Receptor in Prostate Cancer Xenografts Using the Affibody Molecule (111)In-DOTA-Z(IGF1R:4551)
- 2012
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:1, s. 90-97
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Journal article (peer-reviewed)abstract
- One of the pathways leading to androgen independence in prostate cancer involves upregulation of insulinlike growth factor type 1 receptor (IGF-1R). Radionuclide imaging of IGF-1R in tumors might be used for selection of patients who would most likely benefit from IGF-1R-targeted therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of IGF-1R expression in prostate cancer xenografts using a small nonimmunoglobulin-derived binding protein called an Affibody molecule. Methods: The IGF-1R-binding Z(IGF1R:4551) Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. The binding of radiolabeled Z(IGF1R:4551) to IGF-1R-expressing cells was evaluated in vitro and in vivo. Results: DOTA-Z(IGF1R:4551) can be stably labeled with (111)In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, (111)In-DOTAZ(IGF1R):(4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung, and salivary gland). Receptor saturation experiments demonstrated that targeting of DU-145 prostate cancer xenografts in NMRI nu/nu mice was IGF-1R-specific. The tumor uptake was 1.1 +/- 0.3 percentage injected dose per gram, and the tumor-to-blood ratio was 3.2 +/- 0.2 at 8 h after injection. Conclusion: This study demonstrates the feasibility of in vivo targeting of IGF-1R-expressing prostate cancer xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical tool for stratification of patients with prostate cancer for IGF-1R-targeting therapy.
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| 10. |
- Abdullah, M Ailieen, et al.
(author)
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Building Networks for Delivering Integrated Product-Service Offerings (IPSOs)
- 2010
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In: Industrial product-service systems -IPS². - Linköping : CIRP. - 9789173933810 - 9173933813
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Conference paper (peer-reviewed)abstract
- The paper describes the effect of forming business networks and collaborations for the purpose of developing an Integrated Product-Service Offering (IPSO) using the Product/Service Systems (PSS). The research method is an in-depth case study of a joint venture formed by four companies developing a new technology for chemical extraction from water sludge waste within the pulp and paper industry.Combining literature from PSS, network theories and collaborative product development, this paper puts forward the benefits for SMEs to collaborate in business networks and produce IPSOs when introducing a new technology in an emerging market. The case study shows that working towards the new market would not have been possible if each party acted individually or maintained their traditional buyer-supplieroperator roles, and that IPSOs can reduce the business risk.
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| 11. |
- Ahlgren, Sara, et al.
(author)
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Targeting of HER2-Expressing Tumors Using 111In-ABY-025, a Second-Generation Affibody Molecule with a Fundamentally Reengineered Scaffold
- 2010
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 51:7, s. 1131-1138
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Journal article (peer-reviewed)abstract
- Overexpression of HER2 in breast carcinomas predicts response to trastuzumab therapy. Affibody molecules based on a non-immunoglobulin scaffold have demon-strated high potential for in vivo molecular imaging of HER2-expressing tumors. Re-engineering of the molecular scaffold has led to a second generation of optimized Affibody molecules, having a surface distinctly different from the parental protein domain from staphylococcal protein A. The new tracer showed further increased melting point, stability and overall hydrophilicity compared to the parental molecule, and was shown to be more amenable for chemical peptide synthesis. The goal of this study was to assess potential effects of this extensive re-engineering on HER2 targeting, using ABY-025, a DOTA conjugated variant of the novel tracer. Methods: 111In-ABY-025 was compared with previously evaluated parent HER2-binding Affibody tracers in vitro and in vivo. The in vivo behavior was further evaluated in mice bearing SKOV-3 xenografts, in rats and in cynomolgus macaques. Results: 111In-ABY-025 bound specifically to HER2 in vitro and in vivo. Direct comparison with the previous generation of HER2-binding tracers showed that ABY-025 retained excellent targeting properties. Rapid blood clearance was shown in mice, rats and macaques. A highly specific tumor uptake of 16.7 ± 2.5 %IA/g was seen at 4 h after injection. The tumor-to-blood ratio was 6.3 at 0.5 h, 88 at 4 h, and increased up to 3 days after injection. Gamma camera imaging of tumors was already possible 0.5 h after injection. Furthermore, repeated i.v. administration of ABY-025 did not induce antibody formation in rats. Conclusions: The biodistribution of 111In-ABY-025 was in remarkably good agreement with the parent tracers, despite profound re-engineering of the non-binding surface. The molecule displayed rapid blood clearance in all species investigated and excellent targeting capacity in tumor bearing mice, leading to high tumor-to-organ-ratios and high contrast imaging shortly after injection.
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| 12. |
- Altai, Mohamed, et al.
(author)
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188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
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In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
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Journal article (peer-reviewed)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
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| 13. |
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| 14. |
- Altai, Mohamed, et al.
(author)
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Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
- 2014
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
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Journal article (peer-reviewed)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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| 15. |
- Altai, Mohamed, et al.
(author)
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Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
- 2013
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
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Journal article (other academic/artistic)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Berggren, Anna, et al.
(author)
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Små avlopp i kretslopp
- 2012
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Reports (peer-reviewed)abstract
- The certification system has provided the prerequisites for recycling fractions from small-scale sewage systems and larger source-separating sewage system to arable land in a quality-assured and trusted manner. Realisation of these ‘ecocycle solutions’ will be highly dependent upon progress by additional municipalities in establishing facilities for treating and recycling fractions from small-scale sewage systems and larger source-separating sewage systems. Key words: slam, avloppsfraktioner, reningsverk, minireningverk, SPCR 178, EN 12566-3, REVAQ, återföring, näring, näringsämnen, wastewater, sewage, sludge
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| 20. |
- Bjelke, Ulf, et al.
(author)
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Crustacea : Kräftdjur - crustaceans
- 2010
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In: The 2010 Red List of Swedish Species. Rödlistade arter i Sverige 2010. - Uppsala : ArtDatabanken, SLU. - 9789188506351 ; , s. 487-493
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Book chapter (other academic/artistic)
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| 21. |
- Buhot, Yann, et al.
(author)
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Impact of hydroelectric power development on reindeer husbandry: the case of Suorva
- 2010
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In: Rangifer. Report. - 0808-2359. ; , s. 86-86
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Conference paper (other academic/artistic)abstract
- Reindeer husbandry in Sapmi continuously coexists and competes with other land users, such as forestry, tourism, hydroelectric power and mine activities. The impact of water regulation for hydroelectric power, on reindeer herding use is rather unknown. In Sirges reindeer herding community in northern Sweden a large part of their range are affected by hydroelectric power developments, which have forced the reindeer herding to change the use of their ranges. Here we study these changes in relation to the Suorva dam within Lule river system, one of 15 dams within Sirges reindeer husbandry community. We compiled topographic maps from 1890 and 2007 and included the Renbruksplan (reindeer husbandry plan) developed by Sirges reindeer husbandry community. The Renbruksplan consists of the reindeer herder's documentation of seasonal grazing ranges within their reindeer husbandry community, in relation to vegetation type, intensity of use and quality of forage. Using topographic maps the losses of pasture in relation to the regulation of the Suorva dam were calculated using GIS software. The impacts on Unna Tjerusj reindeer herding community north of the dam Suorva are not included in this study. The results of the study showed that after the four water regulations (1923, 1941, 1944 and 1972) the reindeer lost calving areas and autumn pastures composed of birch forest and mires. In Sirges 55 km² has been lost as a direct result of the flooding of grazing areas. This constitutes 6 % of the ranges used during the bare-ground season in the Vaisa-group of Sirges herding ranges. This also includes the loss of important movement areas, which formerly connected seasonal grazing areas along the flooded rivers system and currently force the reindeer to use steeper less productive hillsides above the dam. In conclusion, this study gives a good overview of how water regulation may affect reindeer herding. Due to the losses, the reindeer herders in this area had to change their migration routes and herding routines in relation to use of the calving grounds and the autumn pastures. These losses most likely had negative effects on reindeer husbandry production, because of the lack of good and rich forage during important parts of the grazing season, however this loss cannot be traced today
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| 22. |
- Carlsson-Jonsson, Anna, et al.
(author)
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N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
- 2014
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In: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 738, s. 319-325
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Journal article (peer-reviewed)abstract
- Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
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| 23. |
- Dexlin Mellby, Linda, et al.
(author)
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Design of recombinant antibody microarrays for membrane protein profiling of cell lysates and tissue extracts.
- 2011
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In: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 11, s. 1550-1554
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Journal article (peer-reviewed)abstract
- Generating global protein expression profiles, including also membrane proteins, will be crucial for our understanding of biological processes in health and disease. In this study, we have expanded our antibody microarray technology platform and designed the first human recombinant antibody microarray for membrane proteins targeting crude cell lysates and tissue extracts. We have optimized all key technological parameters and successfully developed a setup for extracting, labeling and analyzing non-fractionated membrane proteomes under non-denaturing conditions. Finally, the platform was also extended and shown to be compatible with simultaneous profiling of both membrane proteins and water-soluble proteins.
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| 24. |
- Dexlin Mellby, Linda, et al.
(author)
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Tissue proteome profiling of preeclamptic placenta using recombinant antibody microarrays
- 2010
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In: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 4:10-11, s. 794-807
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Journal article (peer-reviewed)abstract
- PURPOSE: preeclampsia (PE) is a severe, multi-system pregnancy disorder of yet unknown cause, missing means of treatment, and our fundamental understanding of the disease is still impaired. The purpose of this discovery study was to define candidate placenta tissue protein biomarker signatures to further decipher the molecular features of PE.EXPERIMENTAL DESIGN: we used recombinant antibody microarrays for multiplexed protein expression profiling of preeclamptic placenta tissue (n=25) versus normal placenta (n=11) targeting mainly immunoregulatory water-soluble proteins and membrane proteins. Furthermore, the three known subgroups of PE were profiled, including women with early onset preeclampsia and late onset preeclampsia, as well as women with PE and bilateral notching and intrauterine growth restrictions.RESULTS: the data showed that the first generation of candidate PE-associated placenta tissue protein signatures were delineated, indicating that PE (receiver operating characteristics (ROC) AUC value of 0.83) and the subgroups thereof (ROC AUC values ≤ 0.91) could be distinguished. Notably, the data implied that all subgroups, but preeclampsia with bilateral notching and IUGR, could be further classified into novel subsets (ROC AUC values of 1.0) displaying different inflammatory signatures.CONCLUSIONS AND CLINICAL RELEVANCE: we have taken one step further toward de-convoluting the complex features of PE at the molecular level using affinity proteomics.
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| 25. |
- Fransson, Rebecca, et al.
(author)
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Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues
- 2014
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In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 5:12, s. 1272-1277
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Journal article (peer-reviewed)abstract
- The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.
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