Fluorodeoxyglucose
3077796
225560215
2008-07-14T09:03:20Z
Ckatz
831038
Reverted edits by [[Special:Contributions/Enoch Wong|Enoch Wong]] ([[User talk:Enoch Wong|talk]]) to last version by FitzColinGerald
{{Chembox new
| Name = Fluorodeoxyglucose
| ImageFile = Fluorodeoxyglucose.PNG
<!-- | ImageSize = 200px -->
| ImageName =
| IUPACName = 2-Deoxy-2-fluoro-<small>D</small>-glucose
| OtherNames = 2-Fluoro-2-deoxy-D-glucose<br />FDG
| Section1 = {{Chembox Identifiers
| CASOther = 29702-43-0<br />63503-12-8 (<sup>18</sup>F)
| SMILES = O[C@H](C(CO)O[C@H](O)<br />[C@H]1F)[C@H]1O
}}
| Section2 = {{Chembox Properties
| Formula = C<sub>6</sub>H<sub>11</sub>FO<sub>5</sub>
| MolarMass = 182.15 g/mol
| Density =
| MeltingPt = 170-176 °C
}}
}}
'''Fluorodeoxyglucose''' is a [[glucose]] [[analog (chemistry)|analog]]. Its full chemical name is '''2-fluoro-2-deoxy-D-glucose''', commonly abbreviated to FDG.
FDG is most commonly used in the [[medical imaging]] modality [[positron emission tomography]] (PET): the [[fluorine]] in the FDG molecule is chosen to be the [[positron]]-emitting [[radioactive isotope]] [[fluorine-18]], to produce<sup>18</sup>F-FDG. After FDG is injected into a patient, a PET scanner can form images of the distribution of FDG around the body. The images can be assessed by a [[nuclear medicine]] physician or [[radiologist]] to provide diagnoses of various medical conditions.
==Mechanism of action and metabolic fate==
FDG, as a glucose analog, is taken up by high-glucose-using cells such as brain, kidney, and cancer cells, where phosphorylation prevents the glucose from being released intact. The 2-oxygen in glucose is needed for further glycolysis, so that (in common with [[2-deoxy-D-glucose]]) FDG cannot be further metabolized in cells, and therefore the FDG-6-phosphate formed does not undergo [[glycolysis]] before radioactive decay. As a result, the distribution of<sup>18</sup>F-FDG is a good reflection of the distribution of glucose uptake and [[phosphorylation]] by cells in the body.
Before FDG decays, it is inhibited from metabolic degradation or use, because of the fluorine at the 2' position in the molecule. However, after FDG decays radioactively, its fluorine is converted to <sup>18</sup>O, and after picking up a H<sup>+</sup> from the environment, it becomes glucose-6-phosphate labeled with harmless nonradioactive "heavy oxygen" (oxygen-18) at the 2' position, and is thereafter metabolized normally in the same way as ordinary glucose.
==Applications==
In PET imaging,<sup>18</sup>F-FDG can be used for the assessment of glucose metabolism in the [[heart]] and the [[brain]]. It is also used for imaging tumours in [[oncology]].<sup>18</sup>F-FDG is taken up by cells, phosphorylated by [[hexokinase]] (whose [[mitochondrial]] form is greatly elevated in rapidly-growing malignant tumours),<ref>{{cite journal | title=High Aerobic Glycolysis of Rat Hepatoma Cells in Culture: Role of Mitochondrial Hexokinase | author = Ernesto Bustamante; Peter L. Pedersen | volume = 74 | issue = 9 | pages = 3735 | journal = Proceedings of the National Academy of Sciences | url=http://www.pnas.org/cgi/reprint/74/9/3735 | doi=10.1073/pnas.74.9.3735 | year=1977 | pmid=198801}}</ref> and retained by tissues with high metabolic activity, such as most types of malignant tumours. As a result FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in [[Hodgkin's disease]], [[non-Hodgkin's lymphoma]], [[colorectal cancer]], [[breast cancer]], [[melanoma]], and [[lung cancer]]. It has also been approved for use in diagnosing [[Alzheimer's disease]].
In body-scanning applications in searching for tumor or metastatic disease, a dose of [[FDG]] in solution (typically 5 to 10 milli[[curie]]s or 200 to 400 [[megabecquerel|MBq]]) is typically injected rapidly into a saline drip running into a vein, in a patient who has been fasting for at least 6 hours, and who has a suitably low blood sugar. (This is a problem for some diabetics; usually PET scanning centers will not administer the isotope to patients with blood glucose levels over about 180 mg/dL = 10 mmol/L, and such patients must be re-scheduled). The patient must then wait about an hour for the sugar to distribute and be taken up into organs which use glucose—a time during which physical activity must be kept to a minimum, in order to minimize uptake of the radioactive sugar in muscles (this causes unwanted artifacts when the organs of interest are inside the body). Then, the patient is placed in the PET scanner for a series of one or more scans which may take from 20 minutes to as long as an hour (often, only about quarter of the body length may be imaged at a time).
==History==
In the 1970s, [[Tatsuo Ido]] at the [[Brookhaven National Laboratory]] was the first to describe the synthesis of<sup>18</sup>F-FDG. The compound was first administered to two normal human volunteers by [[Abass Alavi]] in August, 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ (see history reference below).
==Means of production and distribution==
Because the high energy particle bombardment conditions in the medical [[cyclotron]] which is used to produce<sup>18</sup>F would destroy organic molecules like deoxyglucose or glucose, the radioactive<sup>18</sup>F must be made first as fluoride in the cyclotron. This may be accomplished by bombardment of neon-20 with deuterons, but usually is done by proton bombardment of<sup>18</sup>O-enriched water, causing a (p,n) reaction (neutron knockout, or spallation) in the<sup>18</sup>O to produce<sup>18</sup>F as labeled hydrofluoric acid, HF. The quickly-decaying<sup>18</sup>F<sup>-</sup> (18-fluoride) is then collected and immediately attached to the deoxyglucose in an automated series of chemical reactions in a "hot cell" (radioisotope chemistry preparation chamber). Following this, the labeled FDG compound (with half-life only 109.8 minutes set by the decay of the<sup>18</sup>F) is rapidly shipped to points of use by the fastest possible mode. This may include dedicated small commercial jet services, to extend the reach of PET scanning to centers hundreds of miles away from the cyclotron which produces the radioisotope-labeled compound.
Recently, on-site cyclotrons with integral shielding and portable chemistry stations for making FDG have accompanied PET scanners to remote hospitals. This technology holds some promise in the future, for replacing some of the scramble to transport FDG from site of manufacture to site of use [http://www.medicalimagingmag.com/issues/articles/2003-07_05.asp].
==References==
{{reflist}}
*[http://www.medcyclopaedia.com/library/topics/volume_i/f/fluorodeoxyglucose_fdg_.aspx?s=Fluorodeoxyglucose&scope=&mode=1 GE Health page on FDG].
*[http://tracerkinetics.engr.iupui.edu/ The Conception of FDG-PET Imaging. Abass Alavi and Martin Reivich.]
==Further reading==
* {{cite journal | journal = Semin Nucl Med. | year = 2002 | volume = 32 | issue = 1 | pages = 6–12 | title = Initial and subsequent approach for the synthesis of 18FDG | author = Fowler JS, Ido T | pmid = 11839070 | doi = 10.1053/snuc.2002.29270}}
[[Category:Deoxy sugars]]
[[Category:Monosaccharides]]
[[Category:Neuroimaging]]
[[Category:Organofluorides]]
[[Category:Radiopharmaceuticals]]
[[de:Fluordesoxyglucose]]
[[it:Fluorodesossiglucosio]]
[[pl:Fluoro-deoxy-glukoza]]