Measuring hypoxia and predicting tumor radioresistance with nuclear medicine assays

Chapman, J. D.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Hanks, Gerald E.

doi:10.1016/s0167-8140(97)00186-2

Cited by 158 publications

(77 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data are relevant in terms of which combination therapy one should choose. Since tumor hypoxia may impair the efficacy of cytostatic drugs but particularly radiotherapy (29), those hypoxic cells can be also preferential targets of bioreductive drugs and hypoxia-directed gene therapy (30,31).…”

Section: Discussionmentioning

confidence: 99%

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Casas¹,

Perotti²,

Ortel³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract.We isolated and characterized cell lines resistant to aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) derived from a murine adenocarcinoma and studied cross resistance with other injuries. The most resistant clones were numbers 4 and 8, which exhibited 6.7-and 4.2-fold increase in resistance respectively. Several characteristics were altered in these clones. A 2-fold increase in cell volume, higher cell spreading, and a more fibroblastic, dendritic pattern, were the morphology features that led us to think they could have different adhesive, invasive or metastatic phenotypes. The amount of porphyrins synthesized per cell in the resistant clones was similar to the parental line but, when it was expressed per mg protein, there was a 2-fold decrease, with a higher proportion of hydrophilic porphyrins. These cells were not cross-resistant to photosensitization with Benzoporphyrin derivative and Merocyanine 540, but exhibited a slight resistance to exogenous protoporphyrin IX treatment. Both clones displayed higher protein content and increased number of mitochondria, together with a higher oxygen consumption. The distinctive features found in the resistant lines led as to think how to exploit the changes induced by PDT treatment to target surviving cells. Those hypoxic cells can be also a preferential target of bioreductive drugs and hypoxia-directed gene therapy, and would be sensitive to treatment with other photosensitizers.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Casas¹,

Perotti²,

Ortel³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Various labeled derivatives are PET active. [82][83][84] Alternatively, the immunohistochemical hypoxia technique is particularly attractive because gradients of hypoxia can be visualized and compared with underlying hierarchical structures in tissues and with gene expression on a cell by cell basis (such as blood perfusion, necrosis, proliferation, differentiation, apoptosis or oxygen-regulated protein expression). 85,86 The technique is based on monoclonal and polyclonal antibodies raised against protein adducts of reductively activated 2-nitroimidazoles.…”

Section: Techniques For the Assessment Of Tumor Oxygenationmentioning

confidence: 99%

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

View full text Add to dashboard Cite

This review paper attempts to provide an overview of the principles and techniques that are often termed electron paramagnetic resonance (EPR) oximetry. The paper discusses the potential of such methods and illustrates they have been successfully applied to measure oxygen tension, an essential parameter of the tumor microenvironment. To help the reader understand the motivation for carrying out these measurements, the importance of tumor hypoxia is first discussed: the basic issues of why a tumor is hypoxic, why these hypoxic microenvironments promote processes driving malignant progression and why hypoxia dramatically influences the response of tumors to cytotoxic treatments will be explained. The different methods that have been used to estimate the oxygenation in tumors will be reviewed. To introduce the basics of EPR oximetry, the specificity of in vivo EPR will be discussed by comparing this technique with NMR and MRI. The different types of paramagnetic oxygen sensors will be presented, as well as the methods for recording the information (EPR spectroscopy, EPR imaging, dynamic nuclear polarization). Several applications of EPR for characterizing tumor oxygenation will be illustrated, with a special emphasis on pharmacological interventions that modulate the tumor microenvironment. Finally, the challenges for transposing the method into the clinic will also be discussed.

show abstract

“…Low oxygen pressures yield low numbers of reactive species during radiation therapy that are needed to damage macromolecules and membranes of tumor cells effectively. Consequently, hypoxic tumor cells are 3-5 times more resistant to ionizing radiation compared to well-oxygenated cells (61). Low pHe also inhibits radiotherapy (62) while mysteriously enhancing hyperthermia (63).…”

Section: Clinical Implications Of the Tumor Microenvironmentmentioning

confidence: 99%

Viscoelastic Imaging of Breast Tumor Microenvironment With Ultrasound

Insana

Pellot‐Barakat

Sridhar

et al. 2004

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

Imaging systems are most effective for detection and classification when they exploit contrast mechanisms specific to particular disease processes. A common example is mammography, where the contrast depends on local changes in cell density and the presence of microcalcifications. Unfortunately the specificity for classifying malignant breast disease is relatively low for many current diagnostic techniques. This paper describes a new ultrasonic technique for imaging the viscoelastic properties of breast tissue. The mechanical properties of glandular breast tissue, like most biopolymers, react to mechanical stimuli in a manner specific to the microenvironment of the tissue. Elastic properties allow noninvasive imaging of desmoplasia while viscous properties describe metabolism-dependent features such as pH. These ultrasonic methods are providing new tools for studying disease mechanisms as well as improving diagnosis.

show abstract

Measuring hypoxia and predicting tumor radioresistance with nuclear medicine assays

Cited by 158 publications

References 39 publications

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Tumor cell lines resistant to ALA-mediated photodynamic therapy and possible tools to target surviving cells

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Viscoelastic Imaging of Breast Tumor Microenvironment With Ultrasound

Contact Info

Product

Resources

About