MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management

Morcillo, Miguel A.; Lucas, Ángel García de; Oteo, Marta; Romero, Eduardo; Magro, Natalia; Ibáñez-Moragues, Marta; Martínez, A.; Garaulet, Guillermo; Arroyo, Alicia G.; López-Casas, Pedro P.; Hidalgo, Manuel; Mulero, Francisca; Martı́nez-Torrecuadrada, Jorge L.

doi:10.1155/2018/8382148

Cited by 14 publications

(18 citation statements)

References 46 publications

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“… 42 Morcillo et al using MT1-MMP as an imaging biomarker for pancreas cancer. 43 MT1-MMP has been recognized as a critical mediator of several steps in pancreatic cancer progression and the targeting of MT1-MMP for pancreatic cancer therapeutic intervention can cause significant toxicities. 44 In this study, GEM/ERL NPs were surface decorated with MT1-AF7p.…”

Section: Discussionmentioning

confidence: 99%

<p>Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib</p>

Yin¹,

Yu²,

Zhang³

et al. 2020

DDDT

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Purpose Pancreatic cancer (PCa) is projected to become the second leading cause of cancer-related deaths by 2030. Gemcitabine (GEM) combined with erlotinib (ERL) have been approved by the FDA for locally advanced, unresectable or metastatic pancreatic cancer therapy since 2005. Type-1 matrix metalloproteinase (MT1-MMP) has been recognized as a critical mediator of several steps in PCa progression including activating TGF-β or releasing latent TGF-β from LTBP-1, resulting in increased collagen production and cleavage collagen. Methods In the present research, GEM and ERL co-loaded nanoparticles (GEM/ERL NPs) were prepared. A non-substrate MT1-MMP binding peptide was decorated onto the GEM/ERL NPs surface. Results M-M GEM/ERL NPs exhibited the highest uptake ability (67.65 ± 2.87%), longest half-life period, largest area under the curve, and the best tumor inhibition efficiency (69.81 ± 4.13%). The body weight, blood urine nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of the system were steady when tested in mice model. Conclusion In conclusion, M-M GEM/ERL NPs protected the drugs in the plasma, improved cellular uptake capacity, exhibited the most remarkable tumor cell inhibition ability, and showed the most efficient tumor growth inhibition capacity in vivo. M-M GEM/ERL NPs could be applied as an efficient and safe system for the synergistic combination chemotherapy of PCa.

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Section: Discussionmentioning

confidence: 99%

<p>Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib</p>

Yin¹,

Yu²,

Zhang³

et al. 2020

DDDT

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“…Numerous rodent models have contributed to the understanding of PDAC pathogenesis and thereby, provided opportunities to characterize and detect disease progression from benign to malignant stages with imaging tools. AsPC-1, 105,115 BxPC-3, 47,92,113 Capan-1, 117 Capan-2, 102,110,120 COLO-357, 94,97 MIA PaCa-2, 74,106 Panc-1 95,129 and PL45 cells 108 (KPC) 89,124 and Pdx-1-Cre; LSL-Kras G12D/+ ; Ink4a/Arf −/− . 16,[71][72][73]104 Last mentioned model has been utilized in molecular ultrasound imaging due to the expression of Thy1 or VEGFR2 on its tumor neovasculature.…”

Section: Preclinical Models For Pdac and Pancreatitis Differentiatimentioning

confidence: 99%

“…Of high interest, cleavable peptides allow to assess pathological proteolytic activities occurring within the tumor site. Specific cleavable peptides have been used to detect PDAC by imaging the activity of proteases including matrix metalloproteinases (MMPs), 107,120 urokinase-type plasminogen activator (uPA) 102 and cathepsin E. 145 Particularly, based on an increasing in vivo fluorescence signal intensity Li and co-workers were able to differentiate between normal pancreas, PanIN-I, PanIN-II/ PanIN-III grades and PDAC using cathepsin E cleavable peptide. 145 Additionally, a study compared the in vivo performances of MT1-MMP antibody and MT1-MMP peptide probe for accurate PDAC detection.…”

Section: Peptidesmentioning

confidence: 99%

“…Both probes accumulated in MT1-MMP-expressing tumors, although the antibody-based probe exhibited 25-30-fold higher tumor uptake than the peptide. 120 Other researchers posted that the mutagenesis of key amino acid residues could optimize the binding ability of MT1-MMP-peptide ligand. 146 In breast cancer mouse model, Ren and co-workers enhanced the fluorescence signal in tumor by 3.2-fold compared to the unmodified peptide.…”

Section: Peptidesmentioning

confidence: 99%

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Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer

Jugniot

Bam

Meuillet

et al. 2020

Bioengineering & Transla Med

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Pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis due to silent onset, resistance to therapies, and rapid spreading. Most patients are ineligible for curable surgery as they present with advanced disease at the time of diagnosis. Present diagnostic methods relying on anatomical changes have various limitations including difficulty to discriminate between benign and malignant conditions, invasiveness, the ambiguity of imaging results, or the inability to detect molecular biomarkers of PDAC initiation and progression. Therefore, new imaging technologies with high sensitivity and specificity are critically needed for accurately detecting PDAC and noninvasively characterizing molecular features driving its pathogenesis. Contrast enhanced targeted ultrasound (CETUS) is an upcoming molecular imaging modality that specifically addresses these issues. Unlike anatomical imaging modalities such as CT and MRI, molecular imaging using CETUS is promising for early and accurate detection of PDAC. The use of molecularly targeted microbubbles that bind to neovascular targets can enhance the ultrasound signal specifically from malignant PDAC tissues. This review discusses the current state of diagnostic imaging modalities for pancreatic cancer and places a special focus on ultrasound targetedmicrobubble technology together with its clinical translatability for PDAC detection.

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“…White arrows indicate tumor location. The imaging probe used was [ 89 Zr]Zr-DFO-LEM2/15, a mAb developed against the MT1-MMP metalloproteinase [ 107 ]. Owing to the central role that this metalloproteinase plays in collagen-induced gemcitabine resistance, this probe could be used for the early prediction of resistance to gemcitabine in metastatic PDAC patients.…”

Section: Figurementioning

confidence: 99%

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

González-Gómez

Pazo‐Cid

Sarria

et al. 2021

JCM

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Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”.

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MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management

Cited by 14 publications

References 46 publications

<p>Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib</p>

<p>Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib</p>

Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

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