Novel Matrix Metalloproteinase Inhibitor [18F]Marimastat-Aryltrifluoroborate as a Probe for <i>In vivo</i> Positron Emission Tomography Imaging in Cancer

Keller, Ulrich auf dem; Bellac, Caroline L.; Li, Ying; Lou, Yuanmei; Lange, Philipp F.; Ting, Richard; Harwig, Curtis; Kappelhoff, Reinhild; Dedhar, Shoukat; Adam, Michael J.; Ruth, Thomas J.; Bénard, François; Perrin, David M.; Overall, Christopher M.

doi:10.1158/0008-5472.can-10-1584

Cited by 80 publications

(52 citation statements)

References 24 publications

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“…PET imaging can identify pre-symptomatic biochemical changes in body tissues where no evidence of abnormality is detected using computed tomography (CT) or magnetic resonance imaging (MRI), or before structural changes occur from disease 18, 19 .…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC

Song

Xiao

Wang

et al. 2017

Sci Rep

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To prepare and evaluate a new radiotracer 18F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of 18F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of 18F-IRS in vivo. We also performed 18F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of 18F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 μM of gefitinib. Biodistribution experiments showed an accumulation of 18F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. 18F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. 18F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.

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Section: Introductionmentioning

confidence: 99%

Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC

Song

Xiao

Wang

et al. 2017

Sci Rep

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“…Initial attempts at such probes used small molecule MMP inhibitors conjugated to radiosisotopes e.g. [33]. More recently, a non-inhibitory MMP activatable probe was designed labeled with 18 Fluoride ( 18 F).…”

Section: Utilizing Novel Mmp Activatable Probes For Cancer Imagingmentioning

confidence: 99%

Moving targets: Emerging roles for MMPs in cancer progression and metastasis

2015

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Matrix metalloproteinases have long been associated with cancer. Clinical trials of small molecule inhibitors for this family of enzymes however, were spectacularly unsuccessful in a variety of tumor types. Here, we discuss some of the newer roles that have been uncovered for MMPs in cancer that would not have been targeted with those initial inhibitors or in the patient populations analyzed. We also consider novel ways of using cancer-associated MMP activity for clinical benefit.

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“…Cy5 dicarboxylate (22.3 mg, 0.03 mmol) and boronate (18.6 mg, 0.03 mmol) were synthesized according to procedures that have been reported previously [34,35,36,37,38]. All the other solvents and reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…All the other solvents and reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA). Reagents were added to a round-bottom flask in the following order: Cy5 dicarboxylate (22.3 mg, 0.03 mmol) [34], boronate (18.6 mg, 0.03 mmol) [35,36,37,38], N -(3-Dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC, 8.9 mg, 0.045 mmol, Sigma), 1-Hydroxybenzotriazole hydrate (HOBt, 6.9 mg, 0.045 mmol, Sigma), N , N -Dimethylformamide (DMF, 2 mL, Sigma, HPLC), and pyridine (32 μL, Sigma, St. Louis, MO, USA) were stirred with a magnetic bar overnight and then purified with C18 Reversed Phase LC Column (00G-4253-P0-AX, Phenomenex (Torrance, CA, USA), Luna ® 10 µm C18(2) 100 Å, LC Column 250 × 21.2 mm, water/acetonitrile: 90/10 to 10/90, 20 min, ultrapure water and HPLC acetonitrile (Sigma, St. Louis, MO, USA)). The product fractions eluting between 22.5 min and 25 min were collected, frozen, lyophilized to a green powder, and stored at −80 °C.…”

Section: Methodsmentioning

confidence: 99%

A Conjugate of Pentamethine Cyanine and 18F as a Positron Emission Tomography/Near-Infrared Fluorescence Probe for Multimodality Tumor Imaging

Kommidi

Chen

et al. 2017

IJMS

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The novel synthesis of a dual-modality, pentamethine cyanine (Cy5) fluorescent, 18F positron emission tomography (PET) imaging probe is reported. The probe shows a large extinction coefficient and large quantum yield in the biologically transparent, near-infrared window (650–900 nm) for in vivo fluorescent imaging. This fluorophore bears the isotope, 18F, giving a 18F-PET/near-infrared fluorescent (NIRF), bi-modal imaging probe, that combines the long-term stability of NIRF and the unlimited penetration depth of PET imaging. The bi-modal probe is labeled with 18F in a quick, one-step reaction, which is important in working with the rapid decay of 18F. The bi-modal probe bears a free carboxyl group, highlighting a PET/NIRF synthon that can be conjugated onto many advanced biomolecules for biomarker-specific in vivo dual-modal PET/NIR tumor imaging, confocal histology, and utility in multi-fluorophore, fluorescence-guided surgery. Its potential in vivo biocompatibility is explored in a quick proof-of-principal in vivo study. The dye is delivered to A549 xenograft flank-tumors to generate PET and NIRF signals at the tumor site. The tumor distribution is confirmed in ex vivo gamma counting and imaging. Pentamethine cyanine (Cy5) has the ability to preferentially accumulate in tumor xenografts. We substitute the PET/NIRF probe for Cy5, and explore this phenomenon.

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Novel Matrix Metalloproteinase Inhibitor [18F]Marimastat-Aryltrifluoroborate as a Probe for In vivo Positron Emission Tomography Imaging in Cancer

Cited by 80 publications

References 24 publications

Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC

Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC

Moving targets: Emerging roles for MMPs in cancer progression and metastasis

A Conjugate of Pentamethine Cyanine and 18F as a Positron Emission Tomography/Near-Infrared Fluorescence Probe for Multimodality Tumor Imaging

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