Kristina Westerlund
Royal Institute of Technology
BiophysicsMolecular imagingMolecular biologyAntibodyRadiochemistryChemistryConjugateChelationIn vitroIn vivoPeptide nucleic acidBiodistributionPretargetingSortase ATrastuzumabDOTAAffibody moleculeNuclear medicineRadionuclide therapyPet imagingCancer researchBiochemistryMedicinePharmacology
Publications 21
#2Anders MyrhammarH-Index: 1
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Natural backbone-cyclized proteins have an increased thermostability and resistance towards proteases, characteristics that have sparked interest in head-to-tail cyclization as a method to stability-enhance proteins used in diagnostics and therapeutic applications, for example. In this proof-of principle study, we have produced and investigated a head-to-tail cyclized and HER2-specific ZHER2:342 Affibody dimer. The sortase A-mediated cyclization reaction is highly efficient (>95%) under optimize...
1 CitationsSource
#1Hanna TanoH-Index: 1
#2Maryam OroujeniH-Index: 7
Last. Vladimir TolmachevH-Index: 61
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Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening the PNA pretargeting probes would increase the tumor-to-kidney dose ratio. The primary probe ZHER2:342-SR-HP15 and the complementary secondary probes HP16, HP17, and HP18, containing 9, 12, and 15 nucleobases, respectively, and carrying a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, syn...
2 CitationsSource
#1Anders Myrhammar (KTH: Royal Institute of Technology)H-Index: 1
#2Anzhelika Vorobyeva (Uppsala University)H-Index: 11
Last. Mohamed Altai (Lund University)H-Index: 19
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Radionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, a pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The pretargeting relies on sequential injections of primary, PNA-tagged antibody and secondary, radiolabeled PNA probe, which ar...
2 CitationsSource
#1Ayman AbouzayedH-Index: 4
#2Hanna TanoH-Index: 1
Last. Anna OrlovaH-Index: 53
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The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated...
1 CitationsSource
#1Mohamed Altai (Uppsala University)H-Index: 19
#2Anzhelika Vorobyeva (Uppsala University)H-Index: 11
Last. Kristina Westerlund (KTH: Royal Institute of Technology)H-Index: 7
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Affibody molecules are small engineered scaffold proteins suitable for in vivo tumor targeting. Radionuclide molecular imaging using directly radiolabelled affibody molecules provides excellent imaging. However, affibody molecules have a high renal reabsorption, which complicates their use for radionuclide therapy. The high renal reabsorption is a common problem for the use of engineered scaffold proteins for radionuclide therapy. Affibody-based PNA-mediated pretargeting reduces dramatically the...
2 CitationsSource
#1Christiane Stiller (KTH: Royal Institute of Technology)H-Index: 3
#2Hooman Aghelpasand (KTH: Royal Institute of Technology)H-Index: 3
Last. Amelie Eriksson Karlström (KTH: Royal Institute of Technology)H-Index: 28
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Antibody–DNA conjugates are powerful tools for DNA-assisted protein analysis. Growing usage of these methods demands efficient production of high-quality conjugates. We developed an easy and fast synthesis route yielding covalent antibody–DNA conjugates with a defined conjugation site and low batch-to-batch variability. We utilize the Z domain from protein A, containing the unnatural amino acid 4-benzoylphenylalanine (BPA) for photoaffinity labeling of the antibodies’ Fc region. Z(xBPA) domains ...
9 CitationsSource
#1Kristina Westerlund (KTH: Royal Institute of Technology)H-Index: 7
#2Anzhelika Vorobyeva (Uppsala University)H-Index: 11
Last. Mohamed Altai (Uppsala University)H-Index: 19
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Pretargeting is a promising strategy to reach high imaging contrast in a shorter time than by targeting with directly radiolabeled monoclonal antibodies (mAbs). One of problems in pretargeting is a ...
10 CitationsSource
#1Kristina Westerlund (KTH: Royal Institute of Technology)H-Index: 7
#2Mohamed Altai (Uppsala University)H-Index: 19
Last. Vladimir Tolmachev (Uppsala University)H-Index: 61
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Affibody molecules are small proteins engineered using a nonanti-body scaffold. Radiolabeled Affibody molecules are excellent imaging probes, but their application to radionuclide therapy has been ...
30 CitationsSource
#1Anzhelika Vorobyeva (Uppsala University)H-Index: 11
#2Kristina Westerlund (KTH: Royal Institute of Technology)H-Index: 7
Last. Amelie Eriksson Karlström (KTH: Royal Institute of Technology)H-Index: 28
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Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide ...
7 CitationsSource
Development of a PET Imaging Approach for Selection of Patients for Affibody-Based PNA-Mediated Pretargeted Radionuclide Therapy