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Diagnostic Uses of Radiopharmaceuticals

Diagnostic Uses of Radiopharmaceuticals. Central Nervous System brain two hemispheres four lobs( frontal, parietal, temporal, occipital) cerebellum cerebrum Thalamus (diencephalon) Hypothalamus (diencephalon) Brain stem (medulla, pons, and midbrain). Spinal cord.

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Diagnostic Uses of Radiopharmaceuticals

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  1. Diagnostic Uses of Radiopharmaceuticals • Central Nervous System • brain • two hemispheres • four lobs( frontal, parietal, temporal, occipital) • cerebellum • cerebrum • Thalamus (diencephalon) • Hypothalamus (diencephalon) • Brain stem (medulla, pons, and midbrain)

  2. Spinal cord • Composed of white and gray matter • Extends from medulla/brain stem to 2nd lumbar vertebrae • CSF cerebral spinal fluid-clear colorless fluid that protects the brain from shocks, delivers nutrients, removes waste from brain.

  3. BBB Blood Brain Barrier. • Protects brain from potentially toxic substances from metabolic or dietary substances. • Movement across the BBB is controlled by active transport • Injury to brain caused by disease, trauma, or toxins causes BBB to lose integrity. • Many radiopharmaceuticals depend on specfic transport process

  4. BBB imaging • BBB imaging useful for: primary or metastatic disease, intracranial inflammation, cerebrovascular disease, complications from head trauma. • BBB imaging mainly done today to determine brain death. • MRI or CT have taken much of the brain imaging.

  5. BBB imaging • Radiopharmaceuticals used to perform BBB imaging do not normally cross the BBB • Several Tc99m labeled radiopharmaceuticals can be used to perform BBB imaging. • Tc99m (least desirable) accumulates in the choroid plexus, potassium perchlorate is administered, acting as a blocker

  6. BBB imaging • Tc99m pentetate-DTPA and Tc99m gluceptate-GH better for planar (static) imaging • DTPA/GH do not require pre-treatment of potassium perchlorate. • Flow, Blood pool, and static imaging is typically done for BBB imaging. • 15-30mCi of Tc99m labeled agent is administered

  7. BBB imaging • Symmetric distribution of radiotracer right and left carotid arteries • Visualization of superior sagittal sinus • Normal delay, symmetric uptake around entire skull

  8. BBB imaging • Abnormal distribution • Disruption in BBB from lesion, will increase uptake , and localize in area of pathology. • Brain death, flow in carotids, complete absence of perfusion in middle and anterior cerebral arteries

  9. Brain perfusion imaging • Evaluate functional abnormalities in brain tissue. • Indications : cerebrovascular disease dementia psychiatric disorders seizure disorders head trauma

  10. Brain perfusion imaging • SPECT imaging generally performed. • Brain death is the only exception (static) • Two primary radiopharmaceuticals: • Tc99m exametazime (HMPAO) • Tc99m bicisate (ECD) • Both tracers are lipid soluble and can cross the BBB

  11. Brain perfusion imaging • Tracer has difficulty diffusing back into circulation. • Imaging can be done up to 6 hrs PI • Adult doses: 10-20 mCi • Tc99m bicisate (ECD) imaged 10-15min PI • Tc99m exametazmine (HMPAO) imaged a minimum 1hr PI.

  12. Brain perfusion imaging Patient Preparation • Patient should remain quiet and unstimulated for entire time PI ie: 10-15 min (ECD) 1hr (HMPAO) • Imaging may be delayed for several hours, tracer has no redistribution. • Upon imaging patient head should be secured (tape, velcro) in order to limit movement.

  13. This scan was performed using 29mCi of 99mTc-ECD. The scan shows decreased perfusion in the frontal, parietal, and temporal lobes. This is typical of patients with ischemic brain disease secondary to stroke.

  14. Brain perfusion imaging • SPECT imaging acquired. • Image acquistion typically takes 20-40min. • Single, dual, or triple head camera is used. • Once projection are acquired computer reconstructed images are generated • Transaxial, sagittal, and coronal planes are obtained.

  15. Normal vs Abnormal • Distribution of tracer is symmetrical in both cerebral hemispheres • Blood flow to gray matter is greater it will show greater intensity of tracer. • White matter shows decreased or no uptake of tracer.

  16. Normal vs Abnormal • Acute cerebral infarct is photopenic (no tracer uptake) affected by stroke. • Alzheimer’s disease decreased perfusion in the parietal, temporal, and frontal lobes of both hemispheres • Schizophernia decreased areas of tracer in frontal lobes • Clinically depressed shows decreased uptake over entire cerebral cortex.

  17. Normal vs Abnormal • Manic depression patients have and increased overall tracer uptake.

  18. Diagnosis of Neurological and Psychiatric Disorders with SPECT • Doctors study two kinds of brain SPECT images: Surface Image: Active Image: Full symmetrical activity across cortical surface High activity in cerebellum and visual or occipital cortex • Doctors look for too much/little activity in a certain area, or asymmetry in areas that should be symmetrical.

  19. SPECT Images of Common Neurological and Psychiatric Disorders Alzheimer’s Disease pervasive hypoperfusion Right Sided Stroke Depression increased limbic activity (left) and decreased prefrontal and temporal lobe activity Head Trauma to left PFC - severe aggression problems/violence

  20. SPECT Images of Common Neurological and Psychiatric Disorders ADHD Normally (left) and while performing a concentration task (right) Schizophrenia Before (left) and after (right) medication Alcohol Marijuana Cocaine Heroin

  21. Pharmacological Intervention • Acetazolamide (Diamox) stimulation is used in patients with: >CAD carotid artery disease >cerebralvascular disease >alzheimer’s disease >used as a cerebral vasodilator (normal blood vessels dilate, diseased blood vessels do not) >administered orally or IV

  22. Pharmacologic Intervention • Baseline brain image is obtained without Acetazolamide (Diamox) • 24hrs PI image, 1mg Acetazolamide is administered • 25min PI of Acetazolamide Tc99m exametazime or Tc99m bicisate imaging obtained 15min PI of tc99m • Pre and Post images are compared.

  23. This scan was carried out using 99mTc-ECD. It shows the typical pattern of atrophy found in Alzheimer patients. It can be distinguished from the ischemic disease scan by following up with a scan performed following a Diamox injection. If the perfusion improves, it is more than likely an Alzheimer type disorder. If the infarcted areas become worsened, it would suggest an ischemic disorder.

  24. Brain Death • Acquired with planar (static) imaging • Assess cerebral blood flow (lack of flow indicative of brain death) • Accurate diagnosis essential to discontinue life support or harvesting organs • Static imaging obtained 1-3hrs PI of Tc99m exametazime or Tc99m bicisate

  25. PET Imaging • PET imaging better than routine NM imaging procedures • Fluorine-18 (F18) labeled Fluorodeoxyglucose (FDG) most widely used. • Disadvantage of F18 FDG is availability and short half-life (demands on-site cyclotron, or close proximity to lab)

  26. PET Imaging • Patient must be NPO for 4hrs. • Tracer (20-30 mCi) injected slowly • Patient lies in a dimly lit room for 30-40min • Imaging begins approx. 30min • Patient ask to void frequently post procedure.

  27. 8.6 milliCuries of 18-FluoroDeoxyGlucose were administered intravenously with the patient in a pentobarbital-induced coma. 45 minutes after injection, tomographic images of the head were obtained. PET imaging was repeated after a 2-week interval (with better pharmacologic control of the seizure activity) to assess for change (10.5 mCi FDG).

  28. Cisternography • CSF or cisternography is performed to evaluate the flow of CSF through normal pathways. • In-111 pentetate DTPA is administered into the subarachnoid space. (3rd and 4th lumbar space) • In-111 has two photopeaks 173 and 247 kEv and physical half life of 2.8 days. • Used due to it’s long half life in order to obtain delayed images

  29. Cisternography • 3 types of studies obtained: • Cisternogram- diagnosis of hydrocephalus • Shuntogram- evaluation of patency of ventriculopertoneal shunts. Injection into shunt reservoir (rarely done) • CSF leaks- diagnosis of cerebrospinal fluid leaks.

  30. Cisternography • Cisternogram 4-6hrs PI In-111 should have completed ascent into cisterns • 24hrs PI IN-111 should be seen in subarchnoid spaces surronding cerebral hemisphere and interhemispheric cisterns • Failure of complete ascent is indicative of delayed images at 48 and 72 hrs PI

  31. 6hr 24 hr

  32. Cisternography • CSF leaks cotton swabs (pledgets) are measured for abnormal activity from nose or ears • Imaging site of suspected leak 1-3 hours PI helpful in localizing CSF • Cotton swabs (pledgets) are removed and measured for activity.

  33. Shunt evaluation • Injection directly into ventricular shunts may determine it’s patency • Shunt used to treat cases of normal pressure hydrocephalus • Radiopharmaceutical In-111 DTPA or Tc99m are used. • Persistent uptake of radiopharmaceutical may indicate partial or complete blockage.

  34. Brain dead yet??? • Any questions???

  35. Brain imaging • BBB • diffusible • 99mTc-HMPAO, 99mTc-ECD, 18F-FDG, DOPA • nondifusible • 99mTcO4-, 99mTc-DTPA • HMPAO (Ceretec) stroke, tumor • two steroisomers, and meso ) • TCO4 most not be older than 2hurs • breaks down to less lipophilic form must be used 30min after preparation TLC must be 80% • brain perfusion scan, labeling of leukocytes (MB, PBS) • uptake about 4%., within 1 min, dose 10-20 mCi

  36. The first case is a Brain SPECT scan using 30 mCi 99Tc-ECD. This scan illustrates the effects of chronic alcohol abuse. The scan shows decreased blood flow to the cerebral cortex at the bilateral parietal lobes. Notice that the parietal lobes are affected while sparing the rest of the brain. This is typical of chronic substance abuse.

  37. Brain Scan • Ethyl Cysteinate Dimer • gray to white 2:1, dose 10-20 mCi, • has been used for epileptic foci • Neurolite • longer half life • http://www.uky.edu/Pharmacy/research/spect.html

  38. 123I isopropyl p iodoamphetamine (IMP) • Lipid soluble, crosses the bbb, binds to receptors, 92% extraction, 5% brain, 33% lung, liver 44%, dose 3 mCi, give Lugol’s solution, no longer available in the US

  39. 18- FDG • Metabolic imaging • phosphorylated FDG-6 not a substrate • 68 Ge attenuation correction • 4-10 mCi • during focal seizures (ictal) met increased • interictal (decreased) • brain tumors

  40. Brain Scans • F-DOPA • striatum, carbidopa, nitecapone, 68-Ge • 15-Oyxgen, 15-water, 133-Xe • 11-C methylspiperone • 11-C carfentanil

  41. Cisternography • Rate of formation, flow and resorption of CSF • 111-In-DTPA, 0.5 mCi, lumbar puncture • Nasal plugs (factor 1.5) • http://www2.utmb.edu/otoref/Grnds/CSF-Leaks-9905/CSF-Leaks-9905.pdf • shunt patency (obstructive hydrocephalus)

  42. In-DTPA • Made with 111-In chloride • t1/2 2.8 days • heat for 15 min at 100oC • for cisternography • gastric emptying studies • QC ?

  43. Other Brain Items • Tumors • gliomas, meningiomas, metasatic tumors • cerebrovascular infarts • intracranial abscess • subdural hematoma • Normal pressure phydrocephalus • CSF rhionrrhea

  44. Thyroid • Two lobes • basal metabolism • T3 and T4 • TSH (pituitary gland) • thyrotoxicosis, Graves disease, exophthalmic goiter • myxedema,

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