Discovery, optimization and biodistribution of an Affibody molecule for imaging of CD69.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
27 09 2021
Historique:
received: 20 04 2021
accepted: 19 08 2021
entrez: 28 9 2021
pubmed: 29 9 2021
medline: 29 12 2021
Statut: epublish

Résumé

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

Identifiants

pubmed: 34580321
doi: 10.1038/s41598-021-97694-6
pii: 10.1038/s41598-021-97694-6
pmc: PMC8476556
doi:

Substances chimiques

Antigens, CD 0
Antigens, Differentiation, T-Lymphocyte 0
CD69 antigen 0
Immunoconjugates 0
Indium Radioisotopes 0
Lectins, C-Type 0
Radiopharmaceuticals 0
Recombinant Fusion Proteins 0
Indium-111 E9NGC49E0T

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

19151

Informations de copyright

© 2021. The Author(s).

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Auteurs

Jonas Persson (J)

Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Roslagstullsbacken 21, 10691, Stockholm, Sweden.

Emmi Puuvuori (E)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 75183, Uppsala, Sweden.

Bo Zhang (B)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 75183, Uppsala, Sweden.

Irina Velikyan (I)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 75183, Uppsala, Sweden.

Ola Åberg (O)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 75183, Uppsala, Sweden.

Malin Müller (M)

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Per-Åke Nygren (PÅ)

Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Roslagstullsbacken 21, 10691, Stockholm, Sweden.

Stefan Ståhl (S)

Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Roslagstullsbacken 21, 10691, Stockholm, Sweden.

Olle Korsgren (O)

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Olof Eriksson (O)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 75183, Uppsala, Sweden. olof.eriksson@ilk.uu.se.

John Löfblom (J)

Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Roslagstullsbacken 21, 10691, Stockholm, Sweden. lofblom@kth.se.

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Classifications MeSH