ArticlePloS one2016
Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 42 citations in OpenAlex.
- Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Trial
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- Radioimmunotheragnosis in Cancer Research.Cancers · 2024Review
- In Vivo Detection ofInternational journal of biomedical imaging · 2024Article
- Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy.Molecules (Basel, Switzerland) · 2023Article
- ImmunoPET Directed to the Brain: A New Tool for Preclinical and Clinical Neuroscience.Biomolecules · 2023Review
- Synthesis andBioconjugate chemistry · 2022Article
- Clickable Albumin Nanoparticles for Pretargeted Drug Delivery toward PD-L1 Overexpressing Tumors in Combination Immunotherapy.Bioconjugate chemistry · 2022Article
- Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma.Frontiers in pharmacology · 2022Review
- Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.Frontiers in medicine · 2022Article
- ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.Frontiers in medicine · 2022Review
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- Positron emission tomography imaging withScientific reports · 2021Article
- Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography.Journal of clinical medicine · 2021Review
- A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.Theranostics · 2021Review
- Cell-to-cell communication mediates glioblastoma progression inBiology open · 2020Article
- Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance.International journal of molecular sciences · 2020Review
- Targeting MMP-14 for dual PET and fluorescence imaging of glioma in preclinical models.European journal of nuclear medicine and molecular imaging · 2020Article
- MT1-MMP deficiency leads to defective ependymal cell maturation, impaired ciliogenesis, and hydrocephalus.JCI insight · 2020Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models.
methodsAn anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments.
results89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models.
conclusionA new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In vivo validation showed high-specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM.
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