Anna Orlova
Science for Life Laboratory
BiophysicsMolecular imagingPathologyMolecular biologyReceptorChemistryConjugateIn vitroIn vivoBiodistributionDOTAProstate cancerAffibody moleculeNuclear medicineRadionuclide therapyMoleculeCancer researchMonoclonal antibodyBiochemistryMedicine
Publications 291
#1Olga Bragina (RAS: Russian Academy of Sciences)H-Index: 4
Last. Roman Zelchan (RAS: Russian Academy of Sciences)H-Index: 1
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Radionuclide molecular imaging of human epidermal growth factor type 2 (HER2) expression may enable a non-invasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin G3 is a small (molecular weigh 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this first-in-human study was to evaluate the safety, biodistribution and dosimetry of 99mTc-(HE)3-G3. Methods: Three cohorts of patients with prim...
1 CitationsSource
#1Tianqi Xu (Uppsala University)H-Index: 2
#2Anzhelika Vorobyeva (Uppsala University)H-Index: 11
Last. Vladimir Tolmachev (Uppsala University)H-Index: 61
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Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targ...
1 CitationsSource
#1Sergey M. Deyev (Tomsk Polytechnic University)H-Index: 29
#2Tianqi Xu (Uppsala University)H-Index: 2
Last. Torbjörn Gräslund (KTH: Royal Institute of Technology)H-Index: 21
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The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40–60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and compositio...
1 CitationsSource
#1Vladimir Tolmachev (Tomsk Polytechnic University)H-Index: 61
#2Anna Orlova (Tomsk Polytechnic University)H-Index: 53
Last. Jens Nørkær Sørensen (Uppsala University)H-Index: 66
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Abstract Targeting of human epidermal growth factor type 2 (HER2) using monoclonal antibodies, antibody-drug conjugates and tyrosine kinase inhibitors extends survival of patients with HER2-expressing metastatic breast cancer. High expression of HER2 is a predictive biomarker for such specific treatment. Accurate determination of HER2 expression level is necessary for stratification of patients to targeted therapy. Non-invasive in vivo radionuclide molecular imaging of HER2 has a potential of re...
1 CitationsSource
Radiolabeled Affibody-based targeting agent 177Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin bindi...
2 CitationsSource
#1O. D. Bragina (RAS: Russian Academy of Sciences)H-Index: 1
#2V. I. Chernov (RAS: Russian Academy of Sciences)H-Index: 3
Last. V. M. Tolmachev (Tomsk Polytechnic University)H-Index: 1
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1 CitationsSource
#6Anna Orlova (Tomsk Polytechnic University)H-Index: 53
#7A. V. Medvedeva (RAS: Russian Academy of Sciences)H-Index: 8
Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6. METHODS: Twenty-nine patients with prim...
9 CitationsSource
#1Sara S. RinneH-Index: 8
#2Anna Orlova (Tomsk Polytechnic University)H-Index: 53
Last. Vladimir TolmachevH-Index: 61
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The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for rep...
2 CitationsSource
#1Haozhong DingH-Index: 3
#2Tianqi XuH-Index: 2
Last. Anzhelika VorobyevaH-Index: 11
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Affibody molecules hold great promise as carriers of cytotoxic drugs for cancer therapy due to their typically high affinity, easy production, and inherent control of the drug molecules' loading and spatial arrangement. Here, the impact of increasing the drug load from one to three on the properties of an affibody drug conjugate targeting the human epidermal growth factor receptor 2 (HER2) was investigated. The affibody carrier was recombinantly expressed as a fusion to an albumin-binding domain...
1 CitationsSource