Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25704388&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Semin+Nucl+Med 2015 ; 45 (2): 163-76 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Optimizing Hypoxia Detection and Treatment Strategies #MMPMID25704388
Koch CJ; Evans SM
Semin Nucl Med 2015[Mar]; 45 (2): 163-76 PMID25704388show ga
Clinical studies using Eppendorf® needle sensors have invariably documented the resistance of hypoxic human tumors to therapy. These studies first documented the need for individual patient measurement of hypoxia, since hypoxia varied from tumor-to-tumor. Furthermore, hypoxia in sarcomas & cervical cancer leads to distant metastasis or local/regional spread, respectively. For various reasons, the field has moved away from direct needle-sensor oxygen measurements to indirect assays (HIF-related changes; bioreductive metabolism) and the latter can be imaged non-invasively. Many of hypoxia?s detrimental therapeutic effects are reversible in mice but little treatment-improvement in hypoxic human tumors has been seen. The question is why? What factors cause human tumors to be refractory to anti-hypoxia strategies? We suggest the primary cause to be the complexity of hypoxia formation and its characteristics. Three basic types of hypoxia exist, encompassing various diffusional (distance from perfused vessel), temporal (on/off cycling) and perfusional (blood-flow efficiency) limitations. Surprisingly, there is no current information on their relative prevalence in human tumors and even animal models. This is important because different hypoxia sub-types are predicted to require different diagnostic and therapeutic approaches, but the implications of this remain unknown. Even more challenging, no agreement exists for the best way to measure hypoxia. Some results even suggest that hypoxia is unlikely to be targetable therapeutically. In this review, the authors will revisit various critical aspects of this field that are sometimes forgotten or misrepresented in the recent literature. Since most current non-invasive imaging studies involve PET-isotope-labelled 2-nitroimidazoles, we will emphasize key findings made in our studies using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide] and F18-labelled EF5. These will show the importance of differentiating hypoxia subtypes, optimizing drug pharmacology, ensuring drug and isotope stability, identifying key biochemical and physiological variables in tumors, and suggesting therapeutic strategies that are most likely to succeed.
free
free
free
Semin+Nucl+Med 2015 ; 45 (2): 163-76
