Sökning: WFRF:(Velikyan Irina 1966 )
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Discovery, optimiza...
Discovery, optimization and biodistribution of an Affibody molecule for imaging of CD69
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- Persson, Jonas (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Div Prot Engn, Roslagstullsbacken 21, S-10691 Stockholm, Sweden.
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- Puuvuori, Emmi (författare)
- Uppsala universitet,Translationell avbildning med PET,Science for Life Laboratory, SciLifeLab
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- Zhang, Bo (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Velikyan, Irina, 1966- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Åberg, Ola, 1978- (författare)
- Uppsala universitet,Plattformen för Preklinisk PET-MRI,Science for Life Laboratory, SciLifeLab
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- Müller, Malin (författare)
- Uppsala universitet,Klinisk immunologi
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- Nygren, Per-Åke, 1961- (författare)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Div Prot Engn, Roslagstullsbacken 21, S-10691 Stockholm, Sweden.
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- Ståhl, Stefan (författare)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Div Prot Engn, Roslagstullsbacken 21, S-10691 Stockholm, Sweden.
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- Korsgren, Olle (författare)
- Uppsala universitet,Klinisk immunologi
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- Eriksson, Olof (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Löfblom, John (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Div Prot Engn, Roslagstullsbacken 21, S-10691 Stockholm, Sweden.
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(creator_code:org_t)
- 2021-09-27
- 2021
- Engelska.
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://www.nature.c...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Due to the wide scale of inflammatory processes in different types of disease, more sensitive and specific biomarkers are required to improve prevention and treatment. Cluster of differentiation 69 (CD69) is one of the earliest cell surface proteins expressed by activated leukocytes. Here we characterize and optimize potential new imaging probes, Affibody molecules targeting CD69 for imaging of activated immune cells. Analysis of candidates isolated in a previously performed selection from a Z variant E. coli library to the recombinant extracellular domain of human CD69, identified one cross-reactive Z variant with affinity to murine and human CD69. Affinity maturation was performed by randomization of the primary Z variant, followed by selections from the library. The resulting Z variants were evaluated for affinity towards human and murine CD69 and thermal stability. The in vivo biodistribution was assessed by SPECT/CT in rats following conjugation of the Z variants by a DOTA chelator and radiolabeling with Indium-111. A primary Z variant with a K-d of approximately 50 nM affinity to human and murine CD69 was identified. Affinity maturation generated 5 additional Z variants with improved or similar affinity. All clones exhibited suitable stability. Radiolabeling and in vivo biodistribution in rat demonstrated rapid renal clearance for all variants, while the background uptake and washout varied. The variant Z(CD69:4) had the highest affinity for human and murine CD69 (34 nM) as well as the lowest in vivo background binding. In summary, we describe the discovery, optimization and evaluation of novel Affibody molecules with affinity for CD69. Affibody molecule Z(CD69:4) is suitable for further development for imaging of activated immune cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
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Till lärosätets databas
- Av författaren/redakt...
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Persson, Jonas
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Puuvuori, Emmi
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Zhang, Bo
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Velikyan, Irina, ...
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Åberg, Ola, 1978 ...
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Müller, Malin
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visa fler...
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Nygren, Per-Åke, ...
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Ståhl, Stefan
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Korsgren, Olle
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Eriksson, Olof
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Löfblom, John
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Radiologi och bi ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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Scientific Repor ...
- Av lärosätet
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Kungliga Tekniska Högskolan
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Uppsala universitet