A Peptide-Based Positron Emission Tomography Probe for <i>In Vivo</i> Detection of Caspase Activity in Apoptotic Cells

Hight, Matthew R.; Cheung, Yiu‐Yin; Nickels, Michael L.; Dawson, Eric S.; Zhao, Ping; Saleh, Samir; Buck, Jason R.; Tang, Dominic H.; Washington, Mary Kay; Coffey, Robert J.; Manning, H. Charles

doi:10.1158/1078-0432.ccr-13-2444

Cited by 31 publications

(28 citation statements)

References 47 publications

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“…Moreover, the probe could be used to estimate the clinical response to therapeutics, however the relatively modest uptake and low selectivity are drawbacks of this probe. 406 …”

Section: Activity Based Probesmentioning

confidence: 99%

Small Molecule Active Site Directed Tools for Studying Human Caspases

et al. 2015

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Caspases are proteases of clan CD and were described for the first time more than two decades ago. They play critical roles in the control of regulated cell death pathways including apoptosis and inflammation. Due to their involvement in the development of various diseases like cancer, neurodegenerative diseases or autoimmune disorders, caspases have been intensively investigated as potential drug targets, both in academic and industrial laboratories. This review presents a thorough, deep, and systematic assessment of all technologies developed over the years for the investigation of caspase activity and specificity using substrates and inhibitors, as well as activity based probes, which in recent years have attracted considerable interest due to their usefulness in the investigation of biological functions of this family of enzymes.

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“…Moreover, the probe could be used to estimate the clinical response to therapeutics, however the relatively modest uptake and low selectivity are drawbacks of this probe. 406 …”

Section: Activity Based Probesmentioning

confidence: 99%

Small Molecule Active Site Directed Tools for Studying Human Caspases

et al. 2015

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“…For example, annexin V-conjugated tracers have been used to detect the exposed phosphatidylserine on the outer leaflet of the cell membrane during apoptosis (62,63). Similarly, probes have been developed that can monitor caspase activity (35,(64)(65)(66). For example, a caspase-3-binding radiotracer, [ 18 F]ICMT-11, was recently used to study the induction of apoptosis by chemotherapeutic agents (67).…”

Section: Discussionmentioning

confidence: 99%

Reporter nanoparticle that monitors its anticancer efficacy in real time

Kulkarni

Rao

Natarajan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.T he failure of anticancer therapy is a major cause of mortality (1). Although the current dogma underlying resistance is based on the Darwinian selection of mutations acquired over time under chemotherapy pressure, emerging evidence indicates that anticancer drugs can be rendered ineffective early on by intrinsic or adaptive resistance as a function of tumor heterogeneity (2-4). For example, response rates to first-line chemotherapy treatments in metastatic breast cancer patients range from a dismal 30% to 70%, and patients with disease progression need to be switched to a different drug (5). Similarly, about 40-60% of patients with a wild-type KRAS do not respond to cetuximab (6). The ability to detect early whether a treatment is working or not and to switch, if necessary, to a regimen that is effective can have a significant effect on the outcome as well as quality of life (7,8).Currently, tumor response to therapy is determined using techniques for direct anatomical measurements, such as computed tomography (CT) and magnetic resonance imaging, or indirectly using positron emission tomography with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) to quantify metabolic activity. However, these techniques lack the sensitivity or specificity to enable very early response assessment, and often, clinicopathological and metabolic readouts can be discordant (5, 9, 10). In the case of immunotherapy, for example, a productive immune response (T cell infiltration) and the unimpeded growth of the tumor will both be manifest as progression on the conventional ...

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“…In addition, caspase is a promising target for imaging apoptosis. Hight et al 75 have successfully utilized a peptide-based caspase inhibitor for the quantification of caspase activity by PET. α v β 3 integrin can be targeted to image neovascularization, as it is only expressed by ECs of neovascellum, proliferating VSMCs and activated macrophages.…”

Section: The Formation Of Vulnerable Plaquesmentioning

confidence: 99%

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

Anwaier

Chen

Cao

et al. 2017

IJN

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Despite the fact that technological advancements have been made in diagnosis and treatment, cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity worldwide. Early detection of atherosclerosis (AS), especially vulnerable plaques, plays a crucial role in the prevention of acute coronary syndrome (ACS). Targeting the critical cytokines and molecules that are upregulated during the biological process of AS by in vivo molecular imaging has been widely used in plaque imaging. With their three-dimensional architecture, composition, and abundant terminal functional groups, dendrimers provide a platform for multitargeting and multimodal imaging. Thus, modified dendrimers with the key molecules upregulated in AS plaques will be an innovative attempt to achieve targeted imaging of AS plaques specifically and efficiently. This review was aimed to address some recent works on imaging of AS plaques using various types of image technology and further discuss the applications of dendrimers, an innovative yet seldom used method in imaging of AS plaques due to some limitations and challenges, and we highlight the bright future of the modified dendrimers in characterizing AS plaques.

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A Peptide-Based Positron Emission Tomography Probe for In Vivo Detection of Caspase Activity in Apoptotic Cells

Cited by 31 publications

References 47 publications

Small Molecule Active Site Directed Tools for Studying Human Caspases

Small Molecule Active Site Directed Tools for Studying Human Caspases

Reporter nanoparticle that monitors its anticancer efficacy in real time

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque

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