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== Uses == PET is both a medical and research tool used in pre-clinical and clinical settings. It is used heavily in the imaging of [[tumor]]s and the search for [[metastasis|metastases]] within the field of [[clinical oncology]], and for the clinical diagnosis of certain diffuse brain diseases such as those causing various types of [[dementia]]s. PET is valued as a research tool to learn and enhance knowledge of the normal human brain, heart function, and support drug development. PET is also used in pre-clinical studies using animals. It allows repeated investigations into the same subjects over time, where subjects can act as their own control and substantially reduces the numbers of animals required for a given study. This approach allows research studies to reduce the sample size needed while increasing the statistical quality of its results.{{citation needed|date=November 2023}} Physiological processes lead to [[Anatomy|anatomical]] changes in the body. Since PET is capable of detecting biochemical processes as well as expression of some proteins, PET can provide molecular-level information much before any anatomic changes are visible. PET scanning does this by using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Regional tracer uptake in various anatomic structures can be visualized and relatively quantified in terms of injected positron emitter within a PET scan.{{citation needed|date=November 2023}} PET imaging is best performed using a dedicated PET scanner.{{citation needed|date=May 2025}} It is also possible to acquire PET images using a conventional dual-head [[gamma camera]] fitted with a coincidence detector. The quality of gamma-camera PET imaging is lower, and the scans take longer to acquire. However, this method allows a low-cost on-site solution to institutions with low PET scanning demand. An alternative would be to refer these patients to another center or relying on a visit by a mobile scanner. Alternative methods of [[medical imaging]] include [[single-photon emission computed tomography]] (SPECT), computed tomography (CT), [[magnetic resonance imaging]] (MRI) and [[functional magnetic resonance imaging]] (fMRI), and [[ultrasound]]. SPECT is an imaging technique similar to PET that uses [[radioligand]]s to detect molecules in the body. SPECT is less expensive and provides inferior image quality than PET. === Oncology === [[File:PET-MIPS-anim.gif|thumb|upright|Whole-body PET scan using {{chem|18|F}}-FDG ([[fluorodeoxyglucose]]). The normal brain and kidneys are labeled, and radioactive urine from breakdown of the FDG is seen in the bladder. In addition, a large metastatic tumor mass from colon cancer is seen in the liver.]] PET scanning with the radiotracer [[Fluorodeoxyglucose (18F)|[<sup>18</sup>F]fluorodeoxyglucose]] (FDG) is widely used in clinical oncology. FDG is a [[glucose]] [[analog (chemistry)|analog]] that is taken up by glucose-using cells and phosphorylated by [[hexokinase]] (whose [[mitochondrial]] form is significantly elevated in rapidly growing [[malignant]] tumors).<ref>{{cite journal |vauthors=Bustamante E, Pedersen P |title=High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase |journal=Proc Natl Acad Sci USA |volume=74 |issue=9 |pages=3735–9 |year=1977 |pmid=198801 |doi=10.1073/pnas.74.9.3735 |pmc=431708 |bibcode=1977PNAS...74.3735B|doi-access=free }}</ref> [[Metabolic trapping]] of the radioactive glucose molecule allows the PET scan to be utilized. The concentrations of imaged FDG tracer indicate tissue metabolic activity as it corresponds to the regional glucose uptake. FDG is used to explore the possibility of cancer spreading to other body sites ([[cancer]] [[metastasis]]). These FDG PET scans for detecting cancer metastasis are the most common in standard medical care (representing 90% of current scans). The same tracer may also be used for the diagnosis of types of [[dementia]]. Less often, other [[radioactive tracers]], usually but not always labelled with [[fluorine-18]] (<sup>18</sup>F), are used to image the tissue concentration of different kinds of molecules of interest inside the body.{{citation needed|date=November 2023}} A typical dose of FDG used in an oncological scan has an effective radiation dose of 7.6 [[millisievert|mSv]].<ref name="Exposure">ARSAC – Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and use of Sealed Sources (March 2018 p.35)</ref> Because the hydroxy group that is replaced by fluorine-18 to generate FDG is required for the next step in [[Glycolysis#Sequence of reactions|glucose metabolism]] in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the [[phosphate]] added by hexokinase. This means that FDG is trapped in any cell that takes it up until it decays, since [[phosphorylation|phosphorylated]] sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the normal brain, liver, kidneys, and most cancers, which have a higher glucose uptake than most normal tissue due to the [[Warburg effect (oncology)|Warburg effect]]. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in [[Hodgkin lymphoma]],<ref>{{cite journal | vauthors = Zaucha JM, Chauvie S, Zaucha R, Biggii A, Gallamini A | title = The role of PET/CT in the modern treatment of Hodgkin lymphoma | journal = Cancer Treatment Reviews | volume = 77 | pages = 44–56 | date = July 2019 | pmid = 31260900 | doi = 10.1016/j.ctrv.2019.06.002 | s2cid = 195772317 }}</ref> [[non-Hodgkin lymphoma]],<ref>{{cite journal | vauthors = McCarten KM, Nadel HR, Shulkin BL, Cho SY | title = Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma | journal = Pediatric Radiology | volume = 49 | issue = 11 | pages = 1545–1564 | date = October 2019 | pmid = 31620854 | doi = 10.1007/s00247-019-04529-8 | s2cid = 204707264 }}</ref> and [[lung cancer]].<ref>{{Cite journal| vauthors = Pauls S, Buck AK, Hohl K, Halter G, Hetzel M, Blumstein NM, Glatting G, Krüger S, Sunder-Plassmann L, Möller P, Hombach V | display-authors = 6 |date=2007|title=Improved non-invasive T-Staging in non-small cell lung cancer by integrated <sup>18</sup>F-FDG PET/CT |journal=Nuklearmedizin|volume=46|issue=1|pages=09–14|doi=10.1055/s-0037-1616618| s2cid = 21791308 |issn=0029-5566}}</ref><ref>{{cite book | vauthors = Steinert HC | chapter = PET and PET–CT of Lung Cancer | title = Positron Emission Tomography | volume = 727 | pages = 33–51 | date = 2011 | pmid = 21331927 | doi = 10.1007/978-1-61779-062-1_3 | publisher = Humana Press | isbn = 978-1-61779-061-4 | series = Methods in Molecular Biology }}</ref><ref>{{cite journal | vauthors = Chao F, Zhang H | title = PET/CT in the staging of the non-small-cell lung cancer | journal = Journal of Biomedicine & Biotechnology | volume = 2012 | pages = 783739 | date = 2012 | pmid = 22577296 | pmc = 3346692 | doi = 10.1155/2012/783739 | doi-access = free }}</ref> A 2020 review of research on the use of PET for Hodgkin lymphoma found evidence that negative findings in interim PET scans are linked to higher [[overall survival]] and [[progression-free survival]]; however, the certainty of the available evidence was moderate for survival, and very low for progression-free survival.<ref>{{cite journal | vauthors = Aldin A, Umlauff L, Estcourt LJ, Collins G, Moons KG, Engert A, Kobe C, von Tresckow B, Haque M, Foroutan F, Kreuzberger N, Trivella M, Skoetz N | display-authors = 6 | title = Interim PET–results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD012643 | date = January 2020 | pmid = 31930780 | pmc = 6984446 | doi = 10.1002/14651858.CD012643.pub3 | doi-access = free | collaboration = Cochrane Haematology Group }}</ref> A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, {{anchor|Metomidate}}[[Carbon-11|<sup>11</sup>C]]-labelled [[metomidate]] (11C-metomidate) has been used to detect tumors of [[adrenocortical]] origin.<ref>{{cite journal | vauthors = Khan TS, Sundin A, Juhlin C, Långström B, Bergström M, Eriksson B | title = 11C-metomidate PET imaging of adrenocortical cancer | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 30 | issue = 3 | pages = 403–10 | date = March 2003 | pmid = 12634969 | doi = 10.1007/s00259-002-1025-9 | s2cid = 23744095 }}</ref><ref>{{cite journal | vauthors = Minn H, Salonen A, Friberg J, Roivainen A, Viljanen T, Långsjö J, Salmi J, Välimäki M, Någren K, Nuutila P | display-authors = 6 | title = Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG | journal = Journal of Nuclear Medicine | volume = 45 | issue = 6 | pages = 972–9 | date = June 2004 | pmid = 15181132 | url = http://jnm.snmjournals.org/cgi/content/full/45/6/972 }}</ref> Also, [[fluorodopa]] (FDOPA) PET/CT (also called F-18-DOPA PET/CT) has proven to be a more sensitive alternative to finding and also localizing [[pheochromocytoma]] than the [[iobenguane]] (MIBG) [[MIBG scan|scan]].<ref>{{cite journal | vauthors = Pacak K, Eisenhofer G, Carrasquillo JA, Chen CC, Li ST, Goldstein DS | title = 6-[<sup>18</sup>F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma | journal = Hypertension | volume = 38 | issue = 1 | pages = 6–8 | date = July 2001 | pmid = 11463751 | doi = 10.1161/01.HYP.38.1.6 | doi-access = free }}</ref><ref>{{cite journal|url=https://emedicine.medscape.com/article/379861-overview|title=Pheochromocytoma Imaging: Overview, Radiography, Computed Tomography|date=10 August 2017|via=eMedicine}}</ref><ref name="pmid19862519">{{cite journal | vauthors = Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, Glatting G, Buck AK, Solbach C, Neumaier B, Reske SN, Mottaghy FM | display-authors = 6 | title = Clinical value of <sup>18</sup>F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (<sup>18</sup>F-DOPA PET/CT) for detecting pheochromocytoma | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 37 | issue = 3 | pages = 484–93 | date = March 2010 | pmid = 19862519 | doi = 10.1007/s00259-009-1294-7 | s2cid = 10147392 }}</ref> === Neuroimaging === {{main|Brain positron emission tomography}} ==== Neurology ==== [[File:PET-image.jpg|thumb|A PET scan of the human brain.]] PET imaging with oxygen-15 indirectly measures blood flow to the brain. In this method, increased radioactivity signal indicates increased blood flow which is assumed to correlate with increased brain activity. Because of its two-minute [[half-life]], oxygen-15 must be piped directly from a medical [[cyclotron]] for such uses, which is difficult.<ref>{{cite book |last1=Cherry |first1=Simon R. |title=Physics in Nuclear Medicine |date=2012 |publisher=Saunders |location=Philadelphia |isbn=9781416051985 |page=60 |edition=4th |url=https://books.google.com/books?id=i794wmV6YQkC&pg=PA60}}</ref> PET imaging with FDG takes advantage of the fact that the brain is normally a rapid user of glucose. Standard FDG PET of the brain measures regional glucose use and can be used in neuropathological diagnosis. Brain pathologies such as [[Alzheimer's disease]] (AD) greatly decrease brain metabolism of both glucose and oxygen in tandem. Therefore FDG PET of the brain may also be used to successfully differentiate Alzheimer's disease from other dementing processes, and also to make early diagnoses of Alzheimer's disease. The advantage of FDG PET for these uses is its much wider availability. In addition, some other fluorine-18 based radioactive tracers can be used to detect [[amyloid-beta]] plaques, a potential [[biomarker]] for Alzheimer's in the brain. These include [[Florbetapir (18F)|florbetapir]], [[Flutemetamol (18F)|flutemetamol]], [[Pittsburgh compound B]] (PiB) and [[Florbetaben (18F)|florbetaben]].<ref>{{cite journal |last1=Anand |first1=Keshav |last2=Sabbagh |first2=Marwan |title=Amyloid Imaging: Poised for Integration into Medical Practice |journal=Neurotherapeutics |date=January 2017 |volume=14 |issue=1 |pages=54–61 |doi=10.1007/s13311-016-0474-y |pmid=27571940 |pmc=5233621|doi-access=free}}</ref> PET imaging with FDG can also be used for localization of "seizure focus". A seizure focus will appear as hypometabolic during an interictal scan.<ref>{{cite journal |last1=Stanescu |first1=Luana |last2=Ishak |first2=Gisele E. |last3=Khanna |first3=Paritosh C. |last4=Biyyam |first4=Deepa R. |last5=Shaw |first5=Dennis W. |last6=Parisi |first6=Marguerite T. |title=FDG PET of the Brain in Pediatric Patients: Imaging Spectrum with MR Imaging Correlation |journal=RadioGraphics |date=September 2013 |volume=33 |issue=5 |pages=1279–1303 |doi=10.1148/rg.335125152 |pmid=24025925|doi-access=free}}</ref> Several radiotracers (i.e. radioligands) have been developed for PET that are [[ligand (biochemistry)|ligands]] for specific [[neuroreceptor]] subtypes such as [<sup>11</sup>C][[raclopride]], [<sup>18</sup>F][[fallypride]] and [<sup>18</sup>F][[desmethoxyfallypride]] for [[dopamine]] [[Dopamine receptor D2|D<sub>2</sub>]]/[[Dopamine receptor D3|D<sub>3</sub>]] receptors; [<sup>11</sup>C][[McN5652]] and [<sup>11</sup>C][[DASB]] for [[serotonin transporter]]s; [<sup>18</sup>F][[mefway]] for serotonin [[5-HT1A receptor|5HT<sub>1A</sub> receptors]]; and [<sup>18</sup>F][[nifene]] for [[nicotinic acetylcholine receptor]]s or [[Enzyme|enzyme substrates]] (e.g. 6-[[FDOPA]] for the [[Aromatic L-amino acid decarboxylase|AADC enzyme]]). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. PET may also be used for the diagnosis of [[hippocampal sclerosis]], which causes epilepsy. FDG, and the less common tracers [[flumazenil]] and [[MPPF]] have been explored for this purpose.<ref>{{cite journal |last1=la Fougère |first1=C. |last2=Rominger |first2=A. |last3=Förster |first3=S. |last4=Geisler |first4=J. |last5=Bartenstein |first5=P. |title=PET and SPECT in epilepsy: A critical review |journal=Epilepsy & Behavior |date=May 2009 |volume=15 |issue=1 |pages=50–55 |doi=10.1016/j.yebeh.2009.02.025 |pmid=19236949|doi-access=free}}</ref><ref>{{cite journal |last1=Hodolic |first1=Marina |last2=Topakian |first2=Raffi |last3=Pichler |first3=Robert |title=18 F-fluorodeoxyglucose and 18 F-flumazenil positron emission tomography in patients with refractory epilepsy |journal=Radiology and Oncology |date=1 September 2016 |volume=50 |issue=3 |pages=247–253 |doi=10.1515/raon-2016-0032 |pmid=27679539 |pmc=5024661}}</ref> If the sclerosis is unilateral (right hippocampus or left hippocampus), FDG uptake can be compared with the healthy side. Even if the diagnosis is difficult with MRI, it may be diagnosed with PET.<ref>{{cite journal |last1=Malmgren |first1=K |last2=Thom |first2=M |title=Hippocampal sclerosis – origins and imaging. |journal=Epilepsia |date=September 2012 |volume=53 |issue=Suppl 4 |pages=19–33 |doi=10.1111/j.1528-1167.2012.03610.x |pmid=22946718|doi-access=free}}</ref><ref>{{cite journal |last1=Cendes |first1=Fernando |title=Neuroimaging in Investigation of Patients With Epilepsy |journal=Continuum |date=June 2013 |volume=19 |issue=3 Epilepsy |pages=623–642 |doi=10.1212/01.CON.0000431379.29065.d3 |pmid=23739101|pmc=10564042 |s2cid=19026991 }}</ref> The development of a number of novel probes for [[Non-invasive procedure|non-invasive]], [[In vivo|''in-vivo'']] PET imaging of neuroaggregate in human brain has brought amyloid imaging close to clinical use. The earliest [[amyloid]] imaging probes included [<sup>18</sup>F]FDDNP,<ref>{{cite journal | vauthors = Agdeppa ED, Kepe V, Liu J, Flores-Torres S, Satyamurthy N, Petric A, Cole GM, Small GW, Huang SC, Barrio JR | display-authors = 6 | title = Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease | journal = The Journal of Neuroscience | volume = 21 | issue = 24 | pages = RC189 | date = December 2001 | pmid = 11734604 | pmc = 6763047 | doi = 10.1523/JNEUROSCI.21-24-j0004.2001 }}</ref> developed at the [[University of California, Los Angeles]], and [[Pittsburgh compound B]] (PiB),<ref name="pmid11814781">{{cite journal |display-authors=6 |vauthors=Mathis CA, Bacskai BJ, Kajdasz ST, McLellan ME, Frosch MP, Hyman BT, Holt DP, Wang Y, Huang GF, Debnath ML, Klunk WE |date=February 2002 |title=A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain |journal=Bioorganic & Medicinal Chemistry Letters |volume=12 |issue=3 |pages=295–8 |doi=10.1016/S0960-894X(01)00734-X |pmid=11814781}}</ref> developed at the [[University of Pittsburgh]]. These probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [<sup>11</sup>C][[polymethylpentene]] (PMP) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for [[acetylcholinesterase]]. Post-mortem examination of AD patients has shown decreased levels of acetylcholinesterase. [<sup>11</sup>C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for [[Stages of death|premortem]] diagnoses of AD and help to monitor AD treatments.<ref>{{cite journal | vauthors = Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, Frey KA, Kilbourn MR | display-authors = 6 | title = In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease | journal = Neurology | volume = 52 | issue = 4 | pages = 691–9 | date = March 1999 | pmid = 10078712 | doi = 10.1212/wnl.52.4.691 | s2cid = 11057426 }}</ref> [[Avid Radiopharmaceuticals]] has developed and commercialized a compound called [[florbetapir]] that uses the longer-lasting [[radionuclide]] fluorine-18 to detect amyloid plaques using PET scans.<ref>[[Gina Kolata|Kolata, Gina]]. [https://www.nytimes.com/2010/06/24/health/research/24scans.html "Promise Seen for Detection of Alzheimer's"], ''[[The New York Times]]'', June 23, 2010. Accessed June 23, 2010.</ref> ==== Neuropsychology or cognitive neuroscience ==== To examine links between specific psychological processes or disorders and brain activity. ==== Psychiatry and neuropsychopharmacology ==== Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to [[dopamine receptor]]s ([[Dopamine receptor D1|D<sub>1</sub>]],<ref>{{cite journal | vauthors = Catafau AM, Searle GE, Bullich S, Gunn RN, Rabiner EA, Herance R, Radua J, Farre M, Laruelle M | display-authors = 6 | title = Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT 2A receptors | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 30 | issue = 5 | pages = 985–93 | date = May 2010 | pmid = 20029452 | pmc = 2949183 | doi = 10.1038/jcbfm.2009.269 | url = }}</ref> D<sub>2</sub>,<ref>{{cite journal | vauthors = Mukherjee J, Christian BT, Dunigan KA, Shi B, Narayanan TK, Satter M, Mantil J | title = Brain imaging of <sup>18</sup>F-fallypride in normal volunteers: blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors | journal = Synapse | volume = 46 | issue = 3 | pages = 170–88 | date = December 2002 | pmid = 12325044 | doi = 10.1002/syn.10128 | s2cid = 24852944 }}</ref><ref>{{cite journal | vauthors = Buchsbaum MS, Christian BT, Lehrer DS, Narayanan TK, Shi B, Mantil J, Kemether E, Oakes TR, Mukherjee J | display-authors = 6 | title = D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia | journal = Schizophrenia Research | volume = 85 | issue = 1–3 | pages = 232–44 | date = July 2006 | pmid = 16713185 | doi = 10.1016/j.schres.2006.03.042 | s2cid = 45446283 }}</ref> reuptake transporter), [[serotonin receptor]]s ([[5-HT1A receptor|5HT<sub>1A</sub>]], [[5-HT2A receptor|5HT<sub>2A</sub>]], reuptake transporter), [[opioid receptor]]s ([[Μ-opioid receptor|mu]] and [[Κ-opioid receptor|kappa]]), [[Acetylcholine receptor|cholinergic receptors]] (nicotinic and [[Muscarinic acetylcholine receptor|muscarinic]]) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in [[schizophrenia]], [[substance abuse]], [[mood disorder]]s and other psychiatric conditions.{{citation needed|date=November 2023}} ==== Stereotactic surgery and radiosurgery ==== PET can also be used in [[image guided surgery]] for the treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions.<ref name="Levivier M, Massager N, Wikler D, Lorenzoni J, Ruiz S, Devriendt D, David P, Desmedt F, Simon S, Van Houtte P, Brotchi J, Goldman S 1146–1154" /> === Cardiology === {{main|Cardiac PET}} [[Cardiology]], [[atherosclerosis]] and vascular disease study: FDG PET can help in identifying [[hibernating myocardium]]. However, the [[cost-effectiveness]] of PET for this role versus [[single-photon emission computed tomography|SPECT]] is unclear. FDG PET imaging of [[atherosclerosis]] to detect patients at risk of [[stroke]] is also feasible. Also, it can help test the efficacy of novel anti-atherosclerosis therapies.<ref name="pmid12057982">{{cite journal | vauthors = Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, Johnström P, Davenport AP, Kirkpatrick PJ, Arch BN, Pickard JD, Weissberg PL | display-authors = 6 | title = Imaging atherosclerotic plaque inflammation with [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography | journal = Circulation | volume = 105 | issue = 23 | pages = 2708–11 | date = June 2002 | pmid = 12057982 | doi = 10.1161/01.CIR.0000020548.60110.76 | doi-access = free }}</ref> === Infectious diseases === Imaging infections with [[molecular imaging]] technologies can improve diagnosis and treatment follow-up. Clinically, PET has been widely used to image bacterial infections using FDG to identify the infection-associated inflammatory response. Three different PET [[contrast agent]]s have been developed to image bacterial infections in vivo are [<sup>18</sup>F][[maltose]],<ref>{{cite journal | vauthors = Gowrishankar G, Namavari M, Jouannot EB, Hoehne A, Reeves R, Hardy J, Gambhir SS | title = Investigation of 6-[<sup>18</sup>F]-fluoromaltose as a novel PET tracer for imaging bacterial infection | journal = PLOS ONE | volume = 9 | issue = 9 | pages = e107951 | date = 2014 | pmid = 25243851 | pmc = 4171493 | doi = 10.1371/journal.pone.0107951 | bibcode = 2014PLoSO...9j7951G | doi-access = free }}</ref> [<sup>18</sup>F]maltohexaose, and [<sup>18</sup>F]2-fluorodeoxy[[sorbitol]] (FDS).<ref>{{cite journal | vauthors = Weinstein EA, Ordonez AA, DeMarco VP, Murawski AM, Pokkali S, MacDonald EM, Klunk M, Mease RC, Pomper MG, Jain SK | display-authors = 6 | title = Imaging Enterobacteriaceae infection in vivo with <sup>18</sup>F-fluorodeoxysorbitol positron emission tomography | journal = Science Translational Medicine | volume = 6 | issue = 259 | pages = 259ra146 | date = October 2014 | pmid = 25338757 | pmc = 4327834 | doi = 10.1126/scitranslmed.3009815 }}</ref> FDS has the added benefit of being able to target only [[Enterobacteriaceae]]. === Bio-distribution studies === In pre-clinical trials, a new drug can be radiolabeled and injected into animals. Such scans are referred to as biodistribution studies. The information regarding drug uptake, retention and elimination over time can be obtained quickly and cost-effectively compare to the older technique of killing and dissecting the animals. Commonly, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an [[Endogeny (biology)|endogenous]] (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance.<ref>{{cite journal | vauthors = Laruelle M | title = Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 20 | issue = 3 | pages = 423–51 | date = March 2000 | pmid = 10724107 | doi = 10.1097/00004647-200003000-00001 | doi-access = free }}</ref> === Small animal imaging === A miniature animal PET has been constructed that is small enough for a fully conscious [[rat]] to be scanned.<ref>{{cite web |url=http://www.chemistry.bnl.gov/ratcap/gallery.html |title=Rat Conscious Animal PET |archive-url=https://web.archive.org/web/20120305072444/http://www.chemistry.bnl.gov/ratcap/gallery.html |archive-date=March 5, 2012 }}</ref> This RatCAP (rat conscious animal PET) allows animals to be scanned without the confounding effects of [[anesthesia]]. PET scanners designed specifically for imaging [[rodent]]s, often referred to as microPET, as well as scanners for small [[primate]]s, are marketed for academic and pharmaceutical research. The scanners are based on microminiature scintillators and amplified [[avalanche photodiode]]s (APDs) through a system that uses single-chip silicon [[Photomultiplier tube|photomultipliers]].<ref name = sciences/> In 2018 the [[UC Davis School of Veterinary Medicine]] became the first veterinary center to employ a small clinical PET scanner as a scanner for clinical (rather than research) animal diagnosis. Because of cost as well as the marginal utility of detecting cancer metastases in companion animals (the primary use of this modality), veterinary PET scanning is expected to be rarely available in the immediate future.{{citation needed|date=April 2020}} === Musculo-skeletal imaging === {{Further|PET for bone imaging}} PET imaging has been used for imaging muscles and bones. FDG is the most commonly used tracer for imaging muscles, and [[NaF-F18]] is the most widely used tracer for imaging bones. ==== Muscles ==== PET is a feasible technique for studying [[skeletal muscle]]s during exercise.<ref>{{cite journal | vauthors = Oi N, Iwaya T, Itoh M, Yamaguchi K, Tobimatsu Y, Fujimoto T | title = FDG-PET imaging of lower extremity muscular activity during level walking | journal = Journal of Orthopaedic Science | volume = 8 | issue = 1 | pages = 55–61 | date = 2003 | pmid = 12560887 | doi = 10.1007/s007760300009 | s2cid = 23698288 }}</ref> Also, PET can provide muscle activation data about deep-lying muscles (such as the [[vastus intermedialis]] and the [[gluteus minimus]]) compared to techniques like [[electromyography]], which can be used only on superficial muscles directly under the skin. However, a disadvantage is that PET provides no timing information about muscle activation because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles.<ref>{{Cite journal |last1=Omi |first1=Rei |last2=Sano |first2=Hirotaka |last3=Ohnuma |first3=Masahiro |last4=Kishimoto |first4=Koshi |last5=Watanuki |first5=Shoichi |last6=Tashiro |first6=Manabu |last7=Itoi |first7=Eiji |date=5 March 2010 |title=Function of the shoulder muscles during arm elevation: an assessment using positron emission tomography |journal=Journal of Anatomy |volume=216 |issue=5 |pages=643–649 |doi=10.1111/j.1469-7580.2010.01212.x |pmid=20298439 |pmc=2872000}}</ref> ==== Bones ==== Together with [<sup>18</sup>F]sodium floride, [[PET for bone imaging]] has been in use for 60 years for measuring regional bone metabolism and blood flow using static and dynamic scans. Researchers have recently started using [<sup>18</sup>F]sodium fluoride to study bone metastasis as well.<ref>{{cite journal |display-authors=6 |vauthors=Azad GK, Siddique M, Taylor B, Green A, O'Doherty J, Gariani J, Blake GM, Mansi J, Goh V, Cook GJ |date=March 2019 |title=<sup>18</sup>F-Fluoride PET/CT SUV? |journal=Journal of Nuclear Medicine |volume=60 |issue=3 |pages=322–327 |doi=10.2967/jnumed.118.208710 |pmc=6424232 |pmid=30042160}}</ref>
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