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Elongation factor was initially developed because of the availability of an antibody stain to verify the distribution in tissue samples. Fluoroerythronitroimidazole was developed as a more hydrophilic derivative of misonidazole that might have more rapid plasma clearance and this could be an imaging advantage.Fluoroetanidazole has binding characteristics similar to FMISO, but has been reported to have less retention in liver and fewer metabolites in animals, but the advantages were not Citrulline sufficient to carry these derivatives to wide clinical testing.Singlephoton emission CT based hypoxia imaging compounds have been introduced with the hope of taking this technology to gamma camera imaging. Direct halogenation of the imidazole ring does not lead to a stable radiopharmaceutical, so the general approach has been to place sugar residues between the nitroimidazole and the radioiodine to stabilize the molecule.These products exhibit minimal deiodination and two derivatives have been evaluated in patients.Introduction of the sugar results in a more watersoluble molecule than misonidazole.This has two consequences: the hydrophilic product clears more rapidly, but its clearance and its background distribution in normoxic tissues is dependent on blood flow.The resulting images have higher contrast when imaging is typically initiated minutes after injection.A simple ratio analysis to infer hypoxia, however, as used for FMISO images, is not valid.The success with radioiodinated Ibuprofen azamycin arabinosides led to attempts to develop technetium derivatives of nitroimidazole.Twodi ffe rentapproaches have been evaluated: both BMS and HL were synthesized and eva luated as hypoxiabased agents.Both of the BMS compounds involve a nitroimidazole group, although it is probably not the dominant influence in determining the biodistribution kinetics of the radiopharmaceuticalandits spec if ic localization in hypoxic tissues.The resulting lack of specificity has led to abandonment of this molecule as a tracer for imaging hypoxia.It also requires a much lower level of O for its reduction and uptake, raising concerns for routine clinical applications radioiodinated azamycin arabinosides and technetiumbased agents.These radiopharmaceuticals, in contrast to PET agents, suffer from lower image contrast and less potential for quantification. Furthermore, the absence of a gold standard for hypoxia evaluation complicates validation of all hypoxia markers, including FMISO, and treatment outcome studies are urgently needed to provide convincing evidence for the clinical value of hypoxia imaging.The altered redox environment associated with hypoxia has led to another class of radiopharmaceuticals for imaging hypoxia.Copper bis are a class of molecules evaluated as freely diffusible but retained blood flow tracers.Several biologic systems have comparable redox potentials: mV for NADH and mV for glutathione.The main advantage of PET is its ability accurately to quantify tissue uptake of the hypoxia tracer, independent of anatomic location of the tumor.Widespread availability of PET scanners and labeled hypoxia tracers in the community make this procedure within reach of every community nuclear medicine center.Although the level of pretherapy hypoxia is an important parameter, its change with treatment gives an even better understanding of the effectiveness of treatment.Recently introduced PETCT scanners provide the opportunity to combine anatomic imaging and functional information.This will not only increase the accuracy of hypoxia imaging but will also allow the images to be incorporated into radiation treatment planning systems to plan and deliver hypoxic subvolume directed radiotherapy boost effectively using intensitymodulated radiotherapy.

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