ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
A peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Development of caspase-3-selective activity-based probes for PET imaging of apoptosis.EJNMMI radiopharmacy and chemistry · 2024Article
- Current trends in luminescence-based assessment of apoptosis.RSC advances · 2023Review
- Activity-based protein profiling: A graphical review.Current research in pharmacology and drug discovery · 2023Review
- Molecular Imaging of Apoptosis: The Case of Caspase-3 Radiotracers.International journal of molecular sciences · 2021Review
- Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review.International journal of molecular sciences · 2021Review
- TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Avenues to molecular imaging of dying cells: Focus on cancer.Medicinal research reviews · 2018Review
- PIK3CAOncotarget · 2017Article
- Evaluation of [Molecular imaging and biology · 2017Article
- Non-Invasive Glutamine PET Reflects Pharmacological Inhibition of BRAFMolecular imaging and biology · 2017Article
- A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque.International journal of nanomedicine · 2017Review
- Reporter nanoparticle that monitors its anticancer efficacy in real time.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer.Molecular imaging and biology · 2016Article
- Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2016Review
- Small Molecule Active Site Directed Tools for Studying Human Caspases.Chemical reviews · 2015Review
- Molecular imaging of plaque vulnerability.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2014Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeApoptosis, or programmed cell death, can be leveraged as a surrogate measure of response to therapeutic interventions in medicine. Cysteine aspartic acid-specific proteases, or caspases, are essential determinants of apoptosis signaling cascades and represent promising targets for molecular imaging. Here, we report development and in vivo validation of [(18)F]4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone ([(18)F]FB-VAD-FMK), a novel peptide-based molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET). EXPERIMENTAL
designSupported by molecular modeling studies and subsequent in vitro assays suggesting probe feasibility, the labeled pan-caspase inhibitory peptide, [(18)F]FB-VAD-FMK, was produced in high radiochemical yield and purity using a simple two-step, radiofluorination. The biodistribution of [(18)F]FB-VAD-FMK in normal tissue and its efficacy to predict response to molecularly targeted therapy in tumors was evaluated using microPET imaging of mouse models of human colorectal cancer.
resultsAccumulation of [(18)F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response to Aurora B kinase inhibition as well as a multidrug regimen that combined an inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in (V600E)BRAF colon cancer. In the latter setting, [(18)F]FB-VAD-FMK PET was also elevated in the tumors of cohorts that exhibited reduction in size.
conclusionsThese studies illuminate [(18)F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine.
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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.