ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2016
Selective Imaging of VEGFR-1 and VEGFR-2 Using 89Zr-Labeled Single-Chain VEGF Mutants.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The prognostic value of [European journal of nuclear medicine and molecular imaging · 2018Trial
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- Novel Molecular Classification of Breast Cancer with PET Imaging.Medicina (Kaunas, Lithuania) · 2024Review
- Visualizing the Tumor Microenvironment: Molecular Imaging Probes Target Extracellular Matrix, Vascular Networks, and Immunosuppressive Cells.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Imaging Early-Stage Metastases Using anMolecular imaging and biology · 2021Article
- The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy.Cancers · 2021Review
- Multi-Scale Imaging of Vascular Pathologies in Cardiovascular Disease.Frontiers in medicine · 2021Review
- Development of Radiotracers for Breast Cancer-The Tumor Microenvironment as an Emerging Target.Cells · 2020Review
- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- PET Imaging of VEGFR with a NovelACS omega · 2020Article
- Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging.Molecular diagnosis & therapy · 2020Article
- Imaging VEGF Receptors and αMolecular imaging and biology · 2018Article
- PET Imaging of Receptor Tyrosine Kinases in Cancer.Molecular cancer therapeutics · 2018Review
- Treatment response assessment with (R)-[EJNMMI research · 2018Article
- Selective Imaging of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Atherosclerotic Lesions in Diabetic and Non-diabetic ApoEMolecular imaging and biology · 2018Article
- Radionuclide imaging of VEGFR2 in glioma vasculature using biparatopic affibody conjugate: proof-of-principle in a murine model.Theranostics · 2018Article
- Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis.International journal of oncology · 2017Article
- Targeting of growth factors in the treatment of hepatocellular carcinoma: The potentials of polysaccharides.Oncology letters · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor-A (VEGF-A) acts via 2 vascular endothelial growth factor receptors, VEGFR-1 and VEGFR-2, that play important and distinct roles in tumor biology. We reasoned that selective imaging of these receptors could provide unique information for diagnostics and for monitoring and optimizing responses to anticancer therapy, including antiangiogenic therapy. Herein, we report the development of 2 first-in-class
methodsFunctionally active mutants of scVEGF (an engineered single-chain version of pan-receptor VEGF-A with an N-terminal cysteine-containing tag for site-specific conjugation), named scVR1 and scVR2 with enhanced affinity to, respectively, VEGFR-1 and VEGFR-2, were constructed. Parental scVEGF and its receptor-specific mutants were site-specifically derivatized with the
resultsAll tracers rapidly accumulated in orthotopic 4T1luc tumors, allowing for the successful PET imaging of the tumors as early as 2 h after injection. Blocking experiments with an excess of pan-receptor or receptor-specific cold proteins indicated that more than 80% of tracer tumor uptake is VEGFR-mediated, whereas uptake in all major organs is not affected by blocking within the margin of error. Critically, blocking experiments indicated that VEGFR-mediated tumor uptake of scVR1/Zr and scVR2/Zr was mediated exclusively by the corresponding receptor, VEGFR-1 or VEGFR-2, respectively. In contrast, uptake of pan-receptor scV/Zr was mediated by both VEGFR-1 and VEGFR-2 at an approximately 2:1 ratio.
conclusionFirst-in-class selective PET tracers for imaging VEGFR-1 and VEGFR-2 were constructed and successfully validated in an orthotopic murine tumor model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.