POSITRON EMISSION TOMOGRAPHY

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POSITRON EMISSION TOMOGRAPHY
Deepika Gupta1, Jayanti Tokas2, Shalini Jain3
and Hariom Yadav3 1Amity University, Noida, UP,
India 2Assistant Scientist, Biochemistry
Department, COBS and Humanities, HAU, Hisar,
Haryana , India 3NIDDK, NIH, Bethesda, MD,
USA Email yadavhariom_at_gmail.com
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Definition

• A positron emission tomography is a nuclear
  medical imaging technique which produces a three
  dimensional image of functional processes in the
  body.

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History of PET scan

• The concept of emission and transmission
  tomography was introduced by David E. Kuhal and
  Roy Edwards in the late 1950s at the university
  of Pennsylvania.
• In the 1970s, Tatsuo Ido at the Brookhaven
  National laboratory was the first to describe the
  synthesis of 18-F FDG, the most commonly used PET
  scanning isotope carrier.
• Now there is not one person who developed the PET
  scan but a whole collection of people have made
  what it is today.

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How it works

• A short lived radioactive tracer isotope, is
  injected in to the living subject (usually in to
  blood circulation) . The tracer is chemically
  incorporated in to a biologically active
  molecule.
• There is a waiting period while the active
  molecule becomes concentrated in tissues of
  interest.
• 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.

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• After traveling up to a few millimeters the
  positron encounter an electron.
• The encounter annihilates them both, producing a
  pair of (gamma) photon moving in opposite
  directions.
• These are detected when they reach scintillator
  in the scanning device creating a burst of light
  which is detected by photomultiplier tubes.
• The technicians can then create an image of the
  parts of your brain, for example which are
  overactive.

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PET SCAN
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Uses

• Detect cancer.
• Determine whether a cancer has spread in the
  body.
• Assess the effectiveness of a treatment plan,
  such as cancer therapy.
• Determine if a cancer has returned after
  treatment.
• Determine blood flow to the heart muscle.
• Determine the effects of a heart attack, or
  myocardial infarction, on areas of the heart.
• Identify areas of the heart muscle that would
  benefit from a procedure such as angioplasty or
  coronary artery bypass surgery (in combination
  with a myocardial perfusion scan).
• Evaluate brain abnormalities, such as tumors,
  memory disorders and seizures and other central
  nervous system disorders.
• To map normal human brain and heart function.

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Combined PET/CT scanner

• To detect structure and function simultaneously.
• Greater detail with a higher level of accuracy
  because both scans are performed at one time
  without the patient having to change positions,
  there is less room for error.
• Greater convenience for the patient who undergoes
  two exams (CT PET) at one sitting, rather than
  at two different times.

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PET/CT FUSION
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Tracer

• Radioisotopes used in PET scans are isotopes of
  carbon, nitrogen,oxygen,gallium and 18F used as a
  substitute of hydrogen.
• Only radioactive forms of natural elements that
  will pass safely through your body and be
  detected by the scanner.
• The type of scanner used depends on what your
  doctor wants to measure. For example, if your
  doctor is looking at the tumor, he might use
  radio labeled glucose (FDG) and watch how it is
  metabolized by the tumor.

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Cyclotron

• Charged particle accelerator.
• Accelerates charged particles in a cycle path and
  these particles gain energy.
• Energetic particles then hit a target material
  get absorbed in to the nucleus, converting the
  target in to the different species.
• For example, a proton of hydrogen, when hits
  18O-water converts it to the 18F-fluoride with
  emission of a neutron other insignificant
  subatomic particles to balance the energy
  equilibrium.

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Hormone

• Chemical substances created by the body that
  control numerous body functions.
• Biological compounds that communicate information
  at a distance. Hormones require specific
  receptors to begin their biological action use
  second messengers to initiate the cellular
  process that uses that information.
• Substances secreted by various organs of the body
  that regulate growth, metabolism, and
  reproduction. They influence the growth and
  activity of cells.
• e.g Atrial natriuretic hormone, thyrotropin,
  growth hormone, androgens, insulin etc.

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Receptors

• Receptors bind with a substance (ligand) for
  which they are structurally shape specific.
• Receptors can be found all over the place
  inside a cell and specially embedded within and
  an integral part of all the membranes that a
  given cell may have.
• Every function, response, interaction, pathway,
  and any other term you might think of that
  concerns the moment to moment existence of a
  cell, is controlled by various receptor/ligand-ind
  uced systems.

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Neuroendocrine system

• Endocrine system is a communication system in
  which hormones act as biochemical messengers.
• Nervous system performs the same functions using
  electrical impulses as messengers.
• Endocrine cells share a number of antigens with
  nerve elements, the term neuroendocrine is also
  used.
• neuroendocrine system is the combination of
  those two systems.

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Neuroendocrine tumors

• Heterogenous group of neoplasms
• Originate from endocrine glands (pititary,
  parathyroids),
• Neuroendocrine (adrenal),
• Endocrine islets within glandular tissue
  (thyroid, pancreatic)
• Cells dispersed between exocrine cells, such as
  endocrine cells of the digestive (GEP) and
  respiratory tracts.
• Produce and secrete a variety of metabolically
  active substances (amines and peptides)
• Cause distinct clinical syndromes, possess
  neuroamine uptake mechanisms and/or specific
  receptors at the cell membrane, such as
  somatostatin (SS) receptors, may occur either
  sporadically or as part of familial syndromes.

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Peptide receptors expressed in GEP-NET

• Somatostatin receptors
• GLP-1 receptors
• Secretin receptors
• Cholecystokininreceptors
• VIP receptors
• Bombesin receptors
• CRF receptors
• CRF receptors
• NPY receptors

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Somatostatin

• Somatostatin consists of a family of a 14-amino
  acid (somatostatin- 140 and a 28-amino acid
  (somatostatin-28) peptide.
• Appears in sevsral organ systems such as central
  nervous system, the hypothalmopituitary system,
  the gastrointestinal tract,the excrine and
  endocrine pancreas and the immune system.
• Somatostatin can be considered to be a
  neurotransmitter, a neurohormone or a local
  hormone acting via autocrine or paracrine
  mechanisms
• Somatostatin and somatostatin analog inhibit
  tumor growth
• Somatostatin has shorter half life (1-2 min)
• Somatostatin analogs- octrotide and lanreotide
  has longer half life (1.5-2 h)

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• Newer analogues such as DOTA-Tyr3 octreotide
  (DOTATOC) have better uptake than octreotide.
• The phenylalanine residue at position 3 is
  replaced by tyrosine, making the compound more
  hydrophilic and increasing the affinity for
  SSTR2, leading to higher uptake in SSTR2-positive
  tumours.

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• SS inhibits the proliferation of both normal and
  tumoral cells by
• Hypophosphorylation of the retinoblastoma gene
  product
• G1 cell cycle arrest
• Apoptosis through SS receptor 3 induced by p53
  and Bax
• Inhibition of growth factors and angiogenesis

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Somatostatin analog

• DOTA-octreotide which has a very high affinity
  for SSTR2.
• DOTA lanreotide has high affinity for SSTR5.
• DOTA-1-NaI-octreotide(DOTANOC), which has shown a
  high affinity for SSTR2, SSTR3 and SSTR5.
• 3 somatostatin analogs, OC, TOC and TATE were
  conjugated to the metal chelator DOTA and labeled
  with the radiometal 111In, 90Y and 67Ga.

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Somatostatin Receptors

• Five human stomatostatin receptor subtypes (sst1,
  sst3, sst4, sst5) have been cloned and partially
  characterised.
• Ssts belong to the family of G protein coupled
  receptors characterised by seven transmembran
  domains.
• Sst3 and sst2 internalize much better than sst1.

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Octreotide

• Brand name Sandostatin
• An octapeptide that mimics natural somatostatin
  pharmacologically
• Potent inhibitor of growth hormone, glucagon, and
  insulin than the natural hormone.
• Since octreotide resembles somatostatin in
  physiological activities, it can
• 1. Inhibit secretion of many hormones,
  such as gastrin, cholecystokinin,
  glucagon, growth hormone, insulin, secretin,
  pancreatic polypeptide, TSH, and vasoactive
  intestinal peptide.
• 2. Reduce secretion of fluids by the
  intestine and pancreas.
• 3. Reduce gastrointestinal motility and
  inhibits contraction of the gallbladder.
• 4. Inhibit the action of certain hormones
  from the anterior pituitary.
• 5. Cause vasocontriction in the blood
  vessels.
• 6. It has also been shown to produce
  analgesic effects, most probably acting as a
  partial agonist at the mu opiod receptor.

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Chelating agent

• An organic (hydrogen and carbon containing)
  compound that binds to charged metallic atoms
  (ions) to increase absorption.
• A chemical compound that has the ability to bind
  strongly with metal ions.
• Additive that can form several bonds to a metal
  ion, in order to deactivate them.Examples of
  chelating agents are EDTA, ethylenediamine,
  phosphite. Syn. Complexing agent.
• DOTA ( 1,4,7,10-tetraazacyclododecane-N,N,,N,,
  ,N,,,-tetraacetic acid) and DTPA (
  Diethylenetriamine penta acetic acid) are two
  commonly used chelating agent in case of
  somatostatin.

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Radiopharmaceuticals

• Drugs containing a radioactive substance, used in
  the diagnosis and treatment of cancer and in pain
  management of bone metastases.
• Medicinal products that are radioactive when used
  in patients. They are primarily used for
  diagnostic purposes. The radiation from the
  radiopharmaceuticals makes it possible to
  photograph the distribution of the medicinal
  product throughout the body.
• It is the study and preparation of
  radiopharmaceuticals, which are radioactive
  pharmaceuticals.

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Important radiopharmaceuticals for neuroendocrine
tumor imaging (somatostatin receptors)

• Gallium DOTA NOC 68Ga-DOTA-NOC
  Radipharmaceutical
• (1,4,7,10-tetraazacyclododecane-1,4,7,10-t
  etraacetic acid-1-Nal3-Octreotide)
• 1,4,7,10-tetraazacyclododecane-N,N,,N,
  ,,N,,,-tetraacetic acid (DOTA)0,Tyr3,octrotide
  (DOTATOC)
• DOTA0,Tyr3octreotate (DOTATATE) which
  has higher affinity for SSTR2.

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Benefits of PET scan

• The information provided by nuclear medicine
  examinations is unique and often unattainable
  using other imaging procedures.
• For many diseases, nuclear medicine scans yield
  the most useful information needed to make a
  diagnosis or to determine appropriate treatment,
  if any.
• Nuclear medicine is less expensive and may yield
  more precise information than exploratory
  surgery.
• By identifying changes in the body at the
  cellular level, PET imaging may detect the early
  onset of disease before it is evident on other
  imaging tests such as CT or MRI.

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Limitations of PET scan

• Time-consuming.
• The resolution of structures of the body with
  nuclear medicine may not be as clear as with
  other imaging techniques, such as CT or MRI.
• PET scanning can give false results if chemical
  balances within the body are not normal.
• Because the radioactive substance decays quickly
  and is effective for only a short period of time,
  it is important for the patient to be on time for
  the appointment and to receive the radioactive
  material at the scheduled time.
• A person who is very obese may not fit into the
  opening of a conventional PET/CT unit.