Article

Imaging the molecular signatures of apoptosis and injury with radiolabeled annexin V.

Department of Radiology/Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA.
Proceedings of the American Thoracic Society 09/2009; 6(5):469-76. DOI: 10.1513/pats.200901-001AW
Source: PubMed

ABSTRACT Annexin V is a ubiquitous intracellular protein in humans that has a variety of intriguing characteristics, including a nanomolar affinity for the membrane-bound constitutive anionic phospholipid known as phosphatidylserine (PS). PS is selectively expressed on the surface of apoptotic or physiologically stressed cells. As such, radiolabeled forms of annexin V have been used in both animal models and human Phase I and Phase II trials to determine if this tracer can be employed as an early surrogate marker of therapeutic efficacy in NSCLC and non-Hodgkin's lymphoma. Many other pulmonary imaging applications of radiolabeled annexin V are also possible, including the detection and monitoring of active pulmonary inflammation and other pathophysiologic stressors in a variety of diseases. In this article, the salient molecular features of apoptosis (and other forms of cell death) that permits imaging with radiolabeled annexin V will be discussed. The latest results from Phase II imaging trials with NSCLC and non-Hodgkin's lymphoma will be also be detailed. Finally, the potential future application of this tracer for the imaging of other pulmonary pathologies will be outlined.

Download full-text

Full-text

Available from: Francis Blankenberg, Feb 24, 2015
0 Followers
 · 
89 Views
  • Source
    • "Irradiation can induce apoptosis and activate the apoptotic pathways (Li et al. 2001; Friesen et al. 2003). Apoptosis is initiated through different pathways, such as the death receptor pathway and the mitochondrial pathway, resulting in a range of apoptotic events from early to late phases (Friesen et al. 2003; Blankenberg 2009). Here, we established an analytic model for assessing indicators which include different subtype immune responses and the induction of apoptosis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: The radioprotective effects of Antrodia cinnamomea (AC) were investigated for understanding the potential usefulness of AC as an adjunct treatment for reducing radiation side effects. Materials and methods: In this study, we determined the ability of AC extracts (AC539) to reduce radiation side effects by analyzing cellular viability in normal mouse spleen immune cells and human cancer cells with different radiosensitivity. We further detected the effect of AC on radiation-induced changes in cytokine- and inflammatory-related gene expressions. Furthermore, apoptosis assay was performed to determine whether AC could inhibit radiation-induced cytotoxicity. Results: We found that an AC dose of 100-150μg/ml, in a time-dependent manner was the most effective in blocking radiation-induced cytotoxicity, in vitro. Radiation-induced cytotoxicity was inhibited in spleen immune cells by 37-56%; however, pretreatment of human colorectal cancer cell line HT-29 with AC did not have any effect on radiation-induced cytotoxicity, while pretreatment of radiosensitive human breast cancer cell lines BT-474 with AC caused a moderate enhancement of radiation-induced damage. Furthermore, AC pretreatment differentially regulated the mRNA expression of several important immunomodulatory genes in response to irradiation in normal and cancer cells. Conclusions: Our data indicate that AC may inhibit important immunoregulatory signaling which could be vital in the avoidance of an over-activated cytotoxic and inflammatory response of the immune system caused by radiation-induced tissue damage. Additionally, AC does not provide a radioprotective effect to tumor cells but instead enhances radiation-induced inflammation and cytotoxicity in cancer.
    International Journal of Radiation Biology 04/2014; DOI:10.3109/09553002.2014.911989 · 1.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Study design: The French system of Samu-Smur allows the admission of patients directly in intensive care unit (ICU). The aim of this study is to examine the utility of the Samu-Smur with regard to such direct admission (DA).Patients and methods: This retrospective study was performed by the Samu of Paris. Patient details were gathered from three reports : namely hospitalisation, transport and regulation reports. These were analysed to decide whether the admission diagnostic was exact, whether the patient’s condition was serious, whether the prehospital treatment justified direct admission into an ICU and whether the management was coherent.Results: In 1997, 409 (31%) cases were studied among the 1,350 admitted patients in ICU. Three groups of patients were classified according to admission to surgical (n = 54), medical (n = 180), cardiological ICU (n = 175). The prehospital diagnosis was confirmed by the hospitalisation report in 91% of patients in the all three groups. The patient’s condition was found to the serious in all cases. Justification of the treatment was respectively found in 96, 88 and 84% of patients. The coherence of management was confirmed in 94, 96 and 89%.Discusssion: This study has shown that Samu-Smur management lead to justifie DA in ICU for all patients in the study. Prospective studies are needed to show the advantages of this strategy in term of speed of management and outcome.
    Annales Françaises d Anesthésie et de Réanimation 11/2000; 19(9):654-661. DOI:10.1016/S0750-7658(00)00294-X · 0.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical use of (18)F-fluorodeoxyglucose (FDG) positron emission tomography in monitoring anticancer treatment is expanding. At the same time a number of radiotracers aiming to image different aspects of tumour biology such as proliferation and apoptosis are being developed. However, the factors determining changes of radiotracer uptake parameters in response to treatment are not well understood. In many cases, cellularity may be the primary determinant of changes of FDG uptake and may confound the interpretation of metabolic changes. Early imaging assessments have in some cases showed transient increases of uptake parameters, commonly termed "flares", which are likely to be unaffected by cellularity and directly reflect pharmacodynamics at a cellular level. In this review a number of settings where molecular imaging "flares" have been described are discussed. Such changes may often be clinically informative and warrant careful study as potential predictive biomarkers.
    Annals of Nuclear Medicine 04/2010; 24(3):137-47. DOI:10.1007/s12149-009-0332-7 · 1.51 Impact Factor
Show more