Imaging Cell Death

Neves, André; Brindle, Kevin M.

doi:10.2967/jnumed.112.114264

Cited by 107 publications

(116 citation statements)

References 25 publications

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“…Apoptosis, also referred to as programmed cell death, is a highly regulated molecular process to remove damaged or functionally impaired cells from the body [1]. Molecular processes during apoptosis include externalization of phosphatidylserine (PS) to the cell membrane surface, activation of caspases 3 and 7, plasma and mitochondrial membrane depolarization and loss of plasma membrane integrity.…”

Section: Introductionmentioning

confidence: 99%

“…This is in contrast to necrosis whereby cells swell, cell membranes become leaky, and cells release their contents into surrounding tissue causing inflammation. Apoptosis plays an important role in cancer development as well as during tumor response to chemo-, radio-and hormonal therapy [1]. Therefore, accurate detection of cell death and molecular imaging of apoptosis is an area of Nuclear Medicine and Biology xxx (2015) xxx-xxx intense research effort in preclinical and clinical oncology.…”

Section: Introductionmentioning

confidence: 99%

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Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

Wuest

Perreault

Kapty

et al. 2015

Nuclear Medicine and Biology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

Wuest

Perreault

Kapty

et al. 2015

Nuclear Medicine and Biology

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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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“…99 One of the limitations of imaging apoptosis is related to its rapid evolution, which renders imaging of the transient apoptotic biomarkers particularly challenging. 100 In fact, in some patients, the ideal temporal window for imaging occurs between 6 and 24 hours after treatment. 101 Thus, concern has been expressed that the relatively small number of cells undergoing apoptosis at any one time and the small time window to have access to the biomarkers during the apoptotic process may limit the widespread use of apoptosis imaging.…”

Section: Imaging Apoptosismentioning

confidence: 99%

PET/CT imaging in cancer: Current applications and future directions

Farwell

Pryma

Mankoff

2014

Cancer

191

120

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Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, 18 F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials. Cancer 2014;120:3433-45.

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Imaging Cell Death

Cited by 107 publications

References 25 publications

Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

Reporter nanoparticle that monitors its anticancer efficacy in real time

PET/CT imaging in cancer: Current applications and future directions

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