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65-528: The effect of the SNP on the binding potential of the human 5-HT 1A neuroreceptor has been assessed with positron emission tomography and the WAY-100635 radioligand , with a study reporting no apparent influence from the SNP. The SNP has been investigated for association with suicide attempts, and psychiatric disorders . One study found an association of the variant with schizophrenia . Some studies associate

130-557: A chest X-ray and 6.5–8 mSv for a CT scan of the chest. Average civil aircrews are exposed to 3 mSv/year, and the whole body occupational dose limit for nuclear energy workers in the US is 50 mSv/year. For scale, see Orders of magnitude (radiation) . For PET-CT scanning, the radiation exposure may be substantial—around 23–26 mSv (for a 70 kg person—dose is likely to be higher for higher body weights). Radionuclides are incorporated either into compounds normally used by

195-460: A PET scanner is its high initial cost and ongoing operating costs. PET is both a medical and research tool used in pre-clinical and clinical settings. It is used heavily in the imaging of tumors and the search for metastases within the field of clinical oncology , and for the clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias . PET is a valuable research tool to learn and enhance our knowledge of

260-399: A Poisson likelihood function but do not involve such a prior. Attenuation correction : Quantitative PET Imaging requires attenuation correction. In these systems attenuation correction is based on a transmission scan using Ge rotating rod source. Transmission scans directly measure attenuation values at 511 keV. Attenuation occurs when photons emitted by the radiotracer inside

325-593: A coincidence pair because their arrival at their respective detectors occurred within a coincidence timing window). In practice, considerable pre-processing of the data is required – correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence). Filtered back projection (FBP) has been frequently used to reconstruct images from

390-522: A concentration L associates with a receptor of concentration or availability R to form a ligand-receptor complex with concentration RL . The binding potential is then the ratio ligand-receptor complex to free ligand at equilibrium and in the limit of L tending to 0, and is given symbol BP: B P = R L L | L ≈ 0 {\displaystyle BP={\frac {RL}{L}}{\bigg |}_{L\approx 0}} This quantity, originally defined by Mintun, describes

455-633: A cyclotron in close proximity to the PET imaging facility. The half-life of fluorine-18 is long enough that radiotracers labeled with fluorine-18 can be manufactured commercially at offsite locations and shipped to imaging centers. Recently rubidium-82 generators have become commercially available. These contain strontium-82, which decays by electron capture to produce positron-emitting rubidium-82. The use of positron-emitting isotopes of metals in PET scans has been reviewed, including elements not listed above, such as lanthanides. The isotope Zr has been applied to

520-611: A given receptor to demonstrate that a drug causes the release of the natural substance. A miniature animal PET has been constructed that is small enough for a fully conscious rat to be scanned. This RatCAP (rat conscious animal PET) allows animals to be scanned without the confounding effects of anesthesia . PET scanners designed specifically for imaging rodents , often referred to as microPET, as well as scanners for small primates , are marketed for academic and pharmaceutical research. The scanners are based on microminiature scintillators and amplified avalanche photodiodes (APDs) through

585-403: A large group of researchers who are active in this field agreed to a consensus nomenclature for these terms, with the intent of making the literature in this field more transparent to non-specialists. The convention involves use of the subscripts p for quantities referred to plasma and ND for quantities referred to the free plus nonspecifically bound concentration in brain (NonDisplaceable). Under

650-417: A medical cyclotron for such uses, which is difficult. 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

715-458: A more sensitive alternative to finding and also localizing pheochromocytoma than the Iobenguane (MIBG) scan . 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 2-minute half-life , oxygen-15 must be piped directly from

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780-657: A potential biomarker for Alzheimer's in the brain. PET imaging with FDG can also be used for localization of "seizure focus". A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [ C] raclopride , [ F] fallypride and [ F] desmethoxyfallypride for dopamine D 2 / D 3 receptors; [ C] McN5652 and [ C] DASB for serotonin transporters ; [ F] mefway for serotonin 5HT 1A receptors ; and [ F] nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6- FDOPA for

845-1082: A substrate for acetylcholinesterase . Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [ C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for premortem diagnoses of AD and help to monitor AD treatments. 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. To examine links between specific psychological processes or disorders and brain activity. 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 receptors ( D 1 , D 2 , reuptake transporter), serotonin receptors ( 5HT 1A , 5HT 2A , reuptake transporter), opioid receptors ( mu and kappa ), cholinergic receptors (nicotinic and muscarinic ) and other sites have been used successfully in studies with human subjects. Studies have been performed examining

910-472: A system that uses single-chip silicon photomultipliers . 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

975-427: A window of 6 to 12 nanoseconds of each other) of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred (i.e., the line of response (LOR)). Analytical techniques, much like the reconstruction of computed tomography (CT) and single-photon emission computed tomography (SPECT) data, are commonly used, although

1040-432: Is FDG, a sugar, for which the waiting period is typically an hour. During the scan, a record of tissue concentration is made as the tracer decays. As the radioisotope undergoes positron emission decay (also known as positive beta decay ), it emits a positron, an antiparticle of the electron with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on

1105-441: Is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is greater computer resource requirements. A further advantage of statistical image reconstruction techniques is that the physical effects that would need to be pre-corrected for when using an analytical reconstruction algorithm, such as scattered photons, random coincidences, attenuation and detector dead-time, can be incorporated into

1170-401: Is an imaging technique similar to PET that uses radioligands to detect molecules in the body. SPECT is less expensive and provides inferior image quality than PET. PET scanning with the radiotracer [ F]fluorodeoxyglucose (FDG) is widely used in clinical oncology. FDG is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form

1235-416: Is determined by the detector timing resolution. As the timing resolution improves, the signal-to-noise ratio (SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems. The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection (typically, within

1300-400: Is expected to be rarely available in the immediate future. 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. PET is a feasible technique for studying skeletal muscles during exercise. Also, PET can provide muscle activation data about deep-lying muscles (such as

1365-500: 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

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1430-564: Is non-invasive, but it does involve exposure to ionizing radiation . FDG, which is now the standard radiotracer used for PET neuroimaging and cancer patient management, has an effective radiation dose of 14  mSv . The amount of radiation in FDG is similar to the effective dose of spending one year in the American city of Denver, Colorado (12.4 mSv/year). For comparison, radiation dosage for other medical procedures range from 0.02 mSv for

1495-464: Is not. There are many publications in which BP denotes B P 2 {\displaystyle BP_{2}} . Generally, if there were no arterial samples ("noninvasive imaging"), BP denotes B P 2 {\displaystyle BP_{2}} . B m a x {\displaystyle B_{max}} : Total density of receptors = R + R L {\displaystyle R+RL} . In PET imaging,

1560-450: Is possible to localize their source along a straight line of coincidence (also called the line of response , or LOR ). In practice, the LOR has a non-zero width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500 picoseconds rather than about 10 nanoseconds , it is possible to localize the event to a segment of a chord , whose length

1625-484: Is practically not always necessary. Two other common measures have been derived, which involve assumptions, but result in measures that should correlate with BP: B P 1 {\displaystyle BP_{1}} and B P 2 {\displaystyle BP_{2}} . While B P 1 {\displaystyle BP_{1}} and B P 2 {\displaystyle BP_{2}} are nonambiguous symbols, BP

1690-444: Is significantly elevated in rapidly growing malignant tumors). 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

1755-494: The 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. If the sclerosis is unilateral (right hippocampus or left hippocampus), FDG uptake can be compared with

1820-492: 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. [ C] polymethylpentene (PMP) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as

1885-439: The cost-effectiveness of PET for this role versus 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. 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

1950-537: The data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult. Coincidence events can be grouped into projection images, called sinograms . The sinograms are sorted by the angle of each view and tilt (for 3D images). The sinogram images are analogous to the projections captured by CT scanners, and can be reconstructed in a similar way. The statistics of data thereby obtained are much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for

2015-692: 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. Together with [ 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 [ F]sodium fluoride to study bone metastasis as well. PET scanning

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2080-517: The G- allele of the polymorphism may have higher personality score for the NEO PI-R Neuroticism and TPQ Harm Avoidance traits. However, not all studies can find a clear association. One study has studied another trait and found higher score on Temperament and Character Inventory self-transcendence scale for G-allele subjects among mood disorder patients. There are a number of other SNPs for

2145-553: The G-allele or GG-genotype with depression . Not all studies show associations between the disorder and the G-allele. In one study of premenstrual dysphoric disorder C/C was found as the high-risk genotype. Several studies have examine the SNP association with medical treatment response, e.g., antidepressant response in mood disorders, e.g., one study reported worse response for G-allele patients. The polymorphism has also been investigated for links to personality traits . Persons with

2210-462: The HTR1A gene: C549T , Ile28Val (rs1799921), Pro16Leu (rs1800041), Gly272Asp (rs1800042) and G294A (rs6294). Binding potential In pharmacokinetics and receptor-ligand kinetics the binding potential (BP) is a combined measure of the density of "available" neuroreceptors and the affinity of a drug to that neuroreceptor. Consider a ligand receptor binding system. Ligand with

2275-427: The amount of radioligand is usually very small (L << Ki, see above), thus B m a x ≈ R {\displaystyle B_{max}\approx R} k 3 {\displaystyle k_{3}} and k 4 {\displaystyle k_{4}} : Transfer rate constants from the two tissue compartment model . NEW NOTATIONAL CONVENTIONS: In Innis et al.,

2340-433: The body are absorbed by intervening tissue between the detector and the emission of the photon. As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, in place of earlier equipment that offered

2405-655: The body such as glucose (or glucose analogues), water , or ammonia , or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as radiotracers . PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radiolabeled with a PET isotope. Thus, the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are continuing to be synthesized. As of this writing there are already dozens in clinical use and hundreds applied in research. In 2020 by far

2470-442: 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. Some fluorine-18 based radioactive tracers used for Alzheimer's include florbetapir , flutemetamol , Pittsburgh compound B (PiB) and florbetaben , which are all used to detect amyloid-beta plaques,

2535-446: The capacity of a receptor to bind ligand. It is a limit (L << Ki) of the general receptor association equation: R L = R ∗ L L + K i {\displaystyle RL={\frac {R*L}{L+Ki}}} and is thus also equivalent to: B P = R K i {\displaystyle BP={\frac {R}{K_{i}}}} These equations apply equally when measuring

2600-539: 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 . As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin lymphoma , non-Hodgkin lymphoma , and lung cancer . A 2020 review of research on

2665-591: The consensus nomenclature, the parameters referred to above as f 1 and BP 1 are now called f p and BP p , while f 2 and BP 2 are called f ND and BP ND . Positron emission tomography Positron emission tomography ( PET ) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes , and in other physiological activities including blood flow , regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on

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2730-431: The healthy side. Even if the diagnosis is difficult with MRI, it may be diagnosed with PET. The development of a number of novel probes for non-invasive , in-vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging close to clinical use. The earliest amyloid imaging probes included [ F]FDDNP developed at the University of California, Los Angeles and Pittsburgh compound B (PiB) developed at

2795-447: The hydroxy group that is replaced by fluorine-18 to generate FDG is required for the next step in 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 phosphorylated sugars, due to their ionic charge, cannot exit from

2860-568: The infection-associated inflammatory response. Three different PET contrast agents have been developed to image bacterial infections in vivo are [ F] maltose , [ F]maltohexaose, and [ F]2-fluorodeoxy sorbitol (FDS). FDS has the added benefit of being able to target only Enterobacteriaceae . 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

2925-537: The isotope ), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron. The encounter annihilates both electron and positron, producing a pair of annihilation ( gamma ) photons moving in approximately opposite directions. These are detected when they reach a scintillator in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of

2990-408: The likelihood model being used in the reconstruction, allowing for additional noise reduction. Iterative reconstruction has also been shown to result in improvements in the resolution of the reconstructed images, since more sophisticated models of the scanner physics can be incorporated into the likelihood model than those used by analytical reconstruction methods, allowing for improved quantification of

3055-467: 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 ( F), are used to image the tissue concentration of different kinds of molecules of interest inside the body. A typical dose of FDG used in an oncological scan has an effective radiation dose of 7.6  mSv . Because

3120-405: The most commonly used radiotracer in clinical PET scanning is the carbohydrate derivative FDG. This radiotracer is used in essentially all scans for oncology and most scans in neurology, thus makes up the large majority of radiotracer (>95%) used in PET and PET-CT scanning. Due to the short half-lives of most positron-emitting radioisotopes, the radiotracers have traditionally been produced using

3185-402: 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

3250-478: 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 endogenous (naturally occurring) substance at

3315-507: The pair of photons moving in approximately opposite directions (they would be exactly opposite in their center of mass frame , but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal "pairs" (i.e. within a timing-window of a few nanoseconds) are ignored. The most significant fraction of electron–positron annihilations results in two 511 keV gamma photons being emitted at almost 180 degrees to each other. Hence, it

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3380-480: The pre-reconstruction corrections described above. Statistical, likelihood-based approaches : Statistical, likelihood-based iterative expectation-maximization algorithms such as the Shepp–Vardi algorithm are now the preferred method of reconstruction. These algorithms compute an estimate of the likely distribution of annihilation events that led to the measured data, based on statistical principles. The advantage

3445-425: The projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. Disadvantages are that shot noise in the raw data is prominent in the reconstructed images, and areas of high tracer uptake tend to form streaks across the image. Also, FBP treats the data deterministically – it does not account for the inherent randomness associated with PET data, thus requiring all

3510-606: The radioactivity distribution. Research has shown that Bayesian methods that involve a Poisson likelihood function and an appropriate prior probability (e.g., a smoothing prior leading to total variation regularization or a Laplacian distribution leading to ℓ 1 {\displaystyle \ell _{1}} -based regularization in a wavelet or other domain), such as via Ulf Grenander 's Sieve estimator or via Bayes penalty methods or via I.J. Good 's roughness method may yield superior performance to expectation-maximization-based methods which involve

3575-573: The related methodology is e.g. given in Laruelle et al. (2002). Estimating BP with PET usually requires that a reference tissue is available. A reference tissue has negligible receptor density and its distribution volume should be the same as the distribution volume in the target region if all receptors were blocked. Although the BP can be measured in a relatively unbiased way by measuring the whole time course of labelled ligand association and blood radioactivity, this

3640-406: The scan, a short-lived radioactive tracer isotope is injected into the living subject (usually into blood circulation). Each tracer atom has been chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest. Then the subject is placed in the imaging scanner. The molecule most commonly used for this purpose

3705-452: The state of these receptors in patients compared to healthy controls in schizophrenia , substance abuse , mood disorders and other psychiatric conditions. PET can also be used in image guided surgery for the treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions. Cardiology , atherosclerosis and vascular disease study: FDG PET can help in identifying hibernating myocardium . However,

3770-406: The statistical quality of its results. Physiological processes lead to 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

3835-402: The target process within the body. For example: PET is a common imaging technique , a medical scintillography technique used in nuclear medicine . A radiopharmaceutical – a radioisotope attached to a drug – is injected into the body as a tracer . When the radiopharmaceutical undergoes beta plus decay , a positron is emitted, and when the positron interacts with an ordinary electron,

3900-473: The total receptor density or the residual receptor density available after binding to second ligand - availability. BP is a pivotal measure in the use of positron emission tomography (PET) to measure the density of "available" receptors, e.g. to assess the occupancy by drugs or to characterize neuropsychiatric diseases (yet, one should keep in mind that binding potential is a combined measure that depends on receptor density as well as on affinity). An overview of

3965-461: The tracking and quantification of molecular antibodies with PET cameras (a method called "immuno-PET"). The biological half-life of antibodies is typically on the order of days, see daclizumab and erenumab by way of example. To visualize and quantify the distribution of such antibodies in the body, the PET isotope Zr is well suited because its physical half-life matches the typical biological half-life of antibodies, see table above. To conduct

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4030-414: The two particles annihilate and two gamma rays are emitted in opposite directions. These gamma rays are detected by two gamma cameras to form a three-dimensional image. PET scanners can incorporate a computed tomography scanner (CT) and are known as PET-CT scanners . PET scan images can be reconstructed using a CT scan performed using one scanner during the same session. One of the disadvantages of

4095-424: 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. PET imaging is best performed using a dedicated PET scanner. 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

4160-594: 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. A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, C -labelled metomidate (11C-metomidate) has been used to detect tumors of adrenocortical origin. Also, fluorodopa (FDOPA) PET/CT (also called F-18-DOPA PET/CT) has proven to be

4225-517: The whole acquisition, while the CT can reach a few billion counts. This contributes to PET images appearing "noisier" than CT. Two major sources of noise in PET are scatter (a detected pair of photons, at least one of which was deflected from its original path by interaction with matter in the field of view, leading to the pair being assigned to an incorrect LOR) and random events (photons originating from two different annihilation events but incorrectly recorded as

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