Tianqi Xu
Uppsala University
Binding siteCytotoxicityBiophysicsMolecular imagingInternalizationMagnetic resonance imagingProtein domainCytotoxic T cellRenal functionSerum albuminPseudomonas exotoxinChemistryConjugateChelationIn vitroIn vivoBinding domainAlbuminDU145Contrast (vision)Epithelial cell adhesion moleculeProbenecidDARPinBiodistributionPretargetingFurosemideMannitolEpidermal growth factor receptorDOTADrugKidneyOvarian cancerGelofusineAffibody moleculeTargeted therapyFusion ToxinPreclinical imagingSpect imagingRadionuclide therapyOvarian carcinomaMoleculeCancer researchReabsorptionNucleobaseCell biologyCancer cellPharmacology
9Publications
2H-index
10Citations
Publications 9
Newest
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...
Source
#1Haozhong DingH-Index: 3
#2Tianqi XuH-Index: 2
Last. Anzhelika VorobyevaH-Index: 11
view all 8 authors...
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...
Source
#1Maryam OroujeniH-Index: 7
#2Tianqi XuH-Index: 2
Last. Vladimir TolmachevH-Index: 61
view all 10 authors...
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies. EGFR-targeted therapy extends survival of patients with disseminated cancers. Radionuclide molecular imaging of EGFR expression would make EGFR-directed treatment more personalized and therefore more efficient. A previous study demonstrated that affibody molecule [68Ga]Ga-DFO-ZEGFR:2377 permits specific positron-emission tomography (PET) imaging of EGFR expression in xenografts at 3 h after injection. We anticipated t...
1 CitationsSource
#1Hanna TanoH-Index: 1
#2Maryam OroujeniH-Index: 7
Last. Vladimir TolmachevH-Index: 61
view all 10 authors...
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...
Source
#1Tianqi XuH-Index: 2
#2Haozhong DingH-Index: 3
Last. Torbjörn GräslundH-Index: 21
view all 7 authors...
The human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in a variety of cancers and therapies targeting HER2 are routinely used in the clinic. Recently, small engineered scaffold proteins, such as affibody molecules, have shown promise as carriers of cytotoxic drugs, and these drug conjugates may become complements or alternatives to the current HER2-targeting therapies. Here, we investigated if a monovalent HER2-binding affibody molecule, ZHER2:2891, fused with a plasma ...
1 CitationsSource
#1Anzhelika VorobyevaH-Index: 11
#2Maryam OroujeniH-Index: 7
Last. Javad GarousiH-Index: 13
view all 8 authors...
Albumin binding domain-Derived Affinity ProTeins (ADAPTs) are small (5 kDa) engineered scaffold proteins that are promising targeting agents for radionuclide-based imaging. A recent clinical study has demonstrated that radiolabeled ADAPTs can efficiently visualize human epidermal growth factor receptor 2 (HER2) expression in breast cancer using SPECT imaging. However, the use of ADAPTs directly labeled with radiometals for targeted radionuclide therapy is limited by their high reabsorption and p...
Source
#1Anzhelika Vorobyeva (Uppsala University)H-Index: 11
#2E. A. Konovalova (RAS: Russian Academy of Sciences)H-Index: 4
Last. Sergey Deyev (Tomsk Polytechnic University)H-Index: 2
view all 10 authors...
Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with 125I using N...
3 CitationsSource
#1Haozhong Ding (KTH: Royal Institute of Technology)H-Index: 3
#2Mohamed Altai (Lund University)H-Index: 19
Last. Torbjörn Gräslund (KTH: Royal Institute of Technology)H-Index: 21
view all 11 authors...
The human epidermal growth factor receptor 2 (HER2) is a clinically validated target for cancer therapy, and targeted therapies are often used in regimens for patients with a high HER2 expression level. Despite the success of current drugs, a number of patients succumb to their disease, which motivates development of novel drugs with other modes of action. We have previously shown that an albumin binding domain-derived affinity protein with specific affinity for HER2, ADAPT6, can be used to deli...
Source
#1Sara S. Rinne (Uppsala University)H-Index: 8
#2Tianqi Xu (Uppsala University)H-Index: 2
Last. Anzhelika Vorobyeva (Uppsala University)H-Index: 11
view all 8 authors...
Human epidermal growth factor receptor type 3 (HER3) is an emerging therapeutic target in several malignancies. To select potential responders to HER3-targeted therapy, radionuclide molecular imaging of HER3 expression using affibody molecules could be performed. Due to physiological expression of HER3 in normal organs, high imaging contrast remains challenging. Due to slow internalization of affibody molecules by cancer cells, we hypothesized that labeling (HE)3-ZHER3:08698-DOTAGA affibody mole...
3 CitationsSource