Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy. 2018

Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation.

UI MeSH Term Description Entries
D007553 Isotope Labeling Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. Isotope Labeling, Stable,Isotope-Coded Affinity Tagging,Isotopically-Coded Affinity Tagging,Affinity Tagging, Isotope-Coded,Affinity Tagging, Isotopically-Coded,Isotope Coded Affinity Tagging,Labeling, Isotope,Labeling, Stable Isotope,Stable Isotope Labeling,Tagging, Isotope-Coded Affinity,Tagging, Isotopically-Coded Affinity
D011878 Radiotherapy The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions. Radiotherapy, Targeted,Targeted Radiotherapy,Radiation Therapy,Radiation Therapy, Targeted,Radiation Treatment,Targeted Radiation Therapy,Radiation Therapies,Radiation Therapies, Targeted,Radiation Treatments,Radiotherapies,Radiotherapies, Targeted,Targeted Radiation Therapies,Targeted Radiotherapies,Therapies, Radiation,Therapies, Targeted Radiation,Therapy, Radiation,Therapy, Targeted Radiation,Treatment, Radiation
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D005260 Female Females
D000072078 Positron Emission Tomography Computed Tomography An imaging technique that combines a POSITRON-EMISSION TOMOGRAPHY (PET) scanner and a CT X RAY scanner. This establishes a precise anatomic localization in the same session. CT PET,CT PET Scan,PET CT Scan,PET-CT,PET-CT Scan,Positron Emission Tomography-Computed Tomography,CT PET Scans,CT Scan, PET,CT Scans, PET,PET CT Scans,PET Scan, CT,PET Scans, CT,PET-CT Scans,Scan, CT PET,Scan, PET CT,Scan, PET-CT,Scans, CT PET,Scans, PET CT,Scans, PET-CT
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018579 Patient Selection Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. Patient Recruitment,Research Subject Recruitment,Selection Criteria,Research Subject Selection,Selection for Treatment,Selection of Research Volunteers,Selection of Subjects,Criteria, Selection,Recruitment, Patient,Recruitment, Research Subject,Recruitments, Research Subject,Research Subject Recruitments,Research Subject Selections,Research Volunteers Selection,Research Volunteers Selections,Selection for Treatments,Selection, Patient,Selection, Research Subject,Selections, Research Subject,Subject Recruitment, Research,Subject Recruitments, Research,Subject Selection, Research,Subject Selections, Research,Subjects Selection,Subjects Selections,Treatment, Selection for,Treatments, Selection for,Volunteers Selection, Research

Related Publications

Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
January 2016, Theranostics,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
November 2017, Nuclear medicine and biology,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
March 2016, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
August 2015, Bioconjugate chemistry,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
September 2010, Current pharmaceutical biotechnology,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
November 2014, European journal of medicinal chemistry,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
July 2018, Journal of labelled compounds & radiopharmaceuticals,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
February 2014, Expert opinion on drug delivery,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
July 2018, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Anzhelika Vorobyeva, and Kristina Westerlund, and Bogdan Mitran, and Mohamed Altai, and Sara Rinne, and Jens Sörensen, and Anna Orlova, and Vladimir Tolmachev, and Amelie Eriksson Karlström
May 2011, European journal of nuclear medicine and molecular imaging,
Copied contents to your clipboard!