In Vivo Detection of Apoptosis

Blankenberg, Francis G.

doi:10.2967/jnumed.107.045898

Cited by 227 publications

(195 citation statements)

References 116 publications

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“…Hence annexin A5-positive cells may potentially escape cell death. 37 We saw a large overlap between PI and annexin A5 staining in the peri-ischemic brain. In an earlier study using the PT model, the largest fraction of apoptotic cells surrounding the infarct core were morphologically identified as neurons.…”

Section: Pt 3hmentioning

confidence: 81%

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Schoknecht

Prager

Vazana

et al. 2014

J Cereb Blood Flow Metab

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Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.

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Section: Pt 3hmentioning

confidence: 81%

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Schoknecht

Prager

Vazana

et al. 2014

J Cereb Blood Flow Metab

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“…23 Active caspase 3 was detected by a polyclonal antibody (Asp 175; Cell Signaling Technology, Beverly, CA). Tissue sections were deparaffinized in xylene and then washed sequentially in 100%, 95%, and 70% ethanol and phosphate-buffered saline solution.…”

Section: Detection Of Apoptosismentioning

confidence: 99%

Rotator Cuff Tear Degeneration and Cell Apoptosis in Smokers Versus Nonsmokers

Lundgreen

Lian

Scott

et al. 2014

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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Purpose-The purpose of this study was to assess the effect of smoking on supraspinatus tendon degeneration, including cellular alterations, proliferation, and apoptosis of tendon cells.Methods-Supraspinatus tendon samples of 10 smokers and 15 nonsmokers with full-thickness tears were compared, focusing on the severity of tendon histopathology including apoptosis (programmed cell death), cellularity, and proliferation. Immunohistochemistry was used to assess the density of apoptotic cells and proliferation. The extent of tendon degeneration was classified according to a revised version of the Bonar tendon histopathology score.Results-The smokers were younger (P = .01). The symptom duration among smokers was longer (P < .05). The supraspinatus tendons from the smokers presented significantly more advanced degenerative changes (Bonar score, 13.5 [interquartile range, 1.4] v 9 [interquartile range, 3]; P < .001). The smokers' tendons showed increased density of apoptotic cells (0.108 [SE, 0.038] v 0.0107 [SE, 0.007]; P = .024) accompanied by reduced tenocyte density (P = .019) and upregulation of proliferative activity (P < .0001). Conclusions-Smoking is associated with worsened supraspinatus tendon histopathology and increased apoptosis.Clinical Relevance-Pronounced degenerative changes, reduced tendon cellularity, and increased apoptosis may indicate reduced tendon healing capacity in smokers.

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“…Several different radiotracers have been developed over the past few years targeting specific events of apoptosis (6). During the apoptotic process, existing cell death-imaging PET and SPECT tracers target externalized aminophospholipids, such as phosphatidylserine ( 99m Tc-annexin V, 99m Tc-labeled C2A domain of synaptotagmin I) and phosphatidylethanolamine ( 99m Tc-labeled duramycin), apoptotic cell membrane imprinting ( 18 F-2-(5-fluoropentyl)-2-methyl malonic acid), and intracellular caspase-3 activation ( 18 F-(S)-1-((1-(2-fluoroethyl)-1H- [1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin [ 18 F-ICMT-11], 18 F-caspasesensitive nanoaggregation tracer [ 18 F-C-SNAT]). Among these, 99m Tc-annexin V is the most widely studied apoptosis-imaging tracer, and its use in the imaging of treatment-induced cell death has been extensively explored in clinical trials of lung cancer, lymphoma, and breast cancer (7).…”

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confidence: 99%

Early Prediction of Tumor Response to Treatment: Preclinical Validation of ^99mTc-Duramycin

et al. 2016

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Noninvasive imaging of cell death can provide an early indication of the efficacy of tumor treatment, aiding clinicians in distinguishing responding patients from nonresponding patients early on. 99m Tcduramycin is a SPECT tracer for cell death imaging. In this study, our aim was to validate the use of 99m Tc-duramycin for imaging the early response of tumors to treatment. Methods: An in vitro binding assay was performed on COLO205 cells treated with 5-fluorouracil (3.1, 31, or 310 μM) and oxaliplatin (0.7 or 7 μM) or radiation (2 or 4.5 Gy). 99m Tc-duramycin cell binding and the levels of cell death were evaluated after treatment. In vivo imaging was performed on 4 groups of CD1-deficient mice bearing COLO205 human colorectal cancer tumors. Each group included 6 tumors. The first group was given irinotecan (100 mg/kg), the second oxaliplatin (5 mg/kg), the third irinotecan (80 mg/kg) plus oxaliplatin (5 mg/kg), and the fourth vehicle (0.9% NaCl and 5% glucose). For radiotherapy studies, COLO205 tumors received 4.5 Gy, 2 fractions of 4.5 Gy in a 24-h interval, pretreatment with an 80 mg/kg dose of irinotecan combined with 2 fractions of 4.5 Gy in a 24-h interval, or no treatment (n 5 5-6/group). Therapy response was evaluated by 99m Tc-duramycin SPECT 24 h after the last dose of therapy. Blocking was used to confirm tracer specificity. Radiotracer uptake in the tumors was validated ex vivo using γ-counting, cleaved caspase-3, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) histology. Results: Chemotherapy and radiotherapy increased 99m Tc-duramycin binding to COLO205 cells in a concentration/ dose-and time-dependent manner, which correlated well with cell death levels (P , 0.05) as analyzed by annexin V and caspase 3/7 activity. In vivo, 99m Tc-duramycin uptake in COLO205 xenografts was increased 2.3-and 2.8-fold (P , 0.001) in mice treated with irinotecan and combination therapy, respectively. Blocking with unlabeled duramycin demonstrated specific binding of the radiotracer. After tumor irradiation with 4.5 Gy, 99m Tc-duramycin uptake in tumors increased significantly (1.24 ± 0.07 vs. 0.57 ± 0.08 percentage injected dose per gram in the unirradiated tumors; P , 0.001). γ-counting of radioactivity in the tumors positively correlated with cleaved caspase-3 (r 5 0.85, P , 0.001) and TUNEL (r 5 0.81, P , 0.001) staining. Conclusion: We demonstrated that 99m Tc-duramycin can be used to image induction of cell death early after chemotherapy and radiotherapy. It holds potential to be translated into clinical use for early assessment of treatment response.

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In Vivo Detection of Apoptosis

Cited by 227 publications

References 116 publications

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Rotator Cuff Tear Degeneration and Cell Apoptosis in Smokers Versus Nonsmokers

Early Prediction of Tumor Response to Treatment: Preclinical Validation of ^99mTc-Duramycin

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In Vivo Detection of Apoptosis

Cited by 227 publications

References 116 publications

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Monitoring Stroke Progression: In Vivo Imaging of Cortical Perfusion, Blood—Brain Barrier Permeability and Cellular Damage in the Rat Photothrombosis Model

Rotator Cuff Tear Degeneration and Cell Apoptosis in Smokers Versus Nonsmokers

Early Prediction of Tumor Response to Treatment: Preclinical Validation of 99mTc-Duramycin

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Early Prediction of Tumor Response to Treatment: Preclinical Validation of ^99mTc-Duramycin