Brown Adipose Tissue strategies to reduce FDG uptake

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Brown Adipose Tissuestrategies to reduce FDG
uptake

• Hossein Jadvar, MD, PhD, MPH, MBA
• Associate Professor of Radiology and Biomedical
  Engineering
• Director of Radiology Research
• University of Southern California
• Los Angeles, California

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BAT Structure and Function

• One of two types of adipose tissue (white and
  brown)
• Contains smaller fat vacuoles, higher number of
  mitochondria, more capillaries than white fat
• Richly innervated by sympathetic nerves (b1, b2,
  b3)
• Uncoupling protein-1 (UCP-1, thermogenin) in
  inner mitochondrial membrane uncouples oxidative
  phosphorylation producing heat energy
  (non-shivering thermogenesis) with ATP provided
  by glycolysis
• Present in newborns (5 body mass) and
  hibernating animals most disappear in adulthood
  (not in mice)
• Contribution to evolutionary success of mammals
• Cannon B et al. Physiol Rev 2004 (Sweden)

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BAT Structure and Function

• Brown Fat White Fat

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BAT Structure and Function

• Hematoxylin-Eosin
  Hematoxylin anti-UCP-1 Ab
• Tatsumi M et al. J Nucl Med 451189-93, 2004.

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BAT Distribution in Humans

• Human depots differently located from than those
  in rodents
• Main depots
• Supraclavicular Fossa (USA-Fat), Axillae, and
  Neck
• Mediastinal
• Paravertebral, Para-aortic, Parahepatic,
  Paracolic
• Suprarenal/Perinephric
• Acutely cold-induced, stimulated by sympathetic
  nervous system
• Almost all mediastinal/suprarenal BAT FDG uptake
  associated with concurrent supraclavicular/paraver
  tebral uptake
• Neck (2.3) gt Paravertebral (1.4) gt Mediastinum
  (0.9) gt Perinephric (0.8), overall (up to 4)
• females gt males children gt adults (15 vs. 2)
  (plt0.01)
• Hany TF et al. Eur J Nucl Med Mol Imaging 2002
  (Switzerland) Yeung HW et al. J Nucl Med 2003
  (MSKCC, NY) Cohade C et al J Nucl Med 2003
  (Johns Hopkins) Kim S et al. Clin Nucl Med 2006
  (Mount Sinai, NY) Nedergaard J et al. Am J
  Physiol 2007.

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Brown Adipose Tissue

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Brown Adipose Tissue

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BAT Effect of Cold and Pharmacologic
Interventions on FDG Uptake

• Female Lewis rats injected with FDG under
  conditions of
• Control (no pre-medication and exposure to cold)
• Exposure to cold (4 C for 4 h)
• Propranolol, or Reserpine, or Dizepam
• Cold Exposure 5x increase in uptake (vs.
  control)
• Propranolol or Reserpine 70 decline in uptake
  (vs. control)
• Diazepam no significant change
• Tatsumi M et al. J Nucl Med 2004 (Johns Hopkins)

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BAT Effect of Fentanyl and Diazepam on FDG
Uptake Gelfand MJ et al. Pediatr Radiol 2005

• 69 pediatric patients received iv Fentanyl, or
  low (0.06 mg/kg) or moderate dose (0.1 mg/kg)
  diazepam prior to PET
• Visual grading BAT FDG uptake
• Fentanyl reduced BAT FDG uptake significantly
  (p0.004)
• Low dose diazepam no effect (p0.98)
• Medium dose diazepam indeterminate
• Lower FDG uptake in agelt10 y compared to agegt10 y
  (p0.02)
• baseline after fentanyl

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BAT Effect of b-adrenergic agonistson FDG Uptake

• Female Lewis rats injected with caffeine,
  ephedrine, or nicotine 30 min before iv FDG
• Increase in BAT FDG uptake compared to control
  rats
• Ephedrine 3.7x
• Nicotine 7.9x
• Nicotine Ephedrine 12.0x
• Caffeine slight (pns)
• Effects blocked by prior b-adrenergic antagonist
• Patients should avoid nicotine, ephedrine before
  FDG PET
• Baba S et al. J Nucl Med 2007 (Johns Hopkins)

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BAT Effect of b-adrenergic antagonistson FDG
Uptake

• 26 patients with FDG PET scans before and after
  propranolol (20 mg po 60 min prior to iv FDG)
• No adverse effects in patients or on tumor FDG
  uptake
• BAT SUVmax (plt0.0001)
• Pre-propranolol 5.52/-2.30
• Post-propranolol 1.39/-0.42
• Post-propranolol scan improved image
  interpretation most notably in the mediastinum
• Similar findings with 80 mg propranolol po 2 hrs
  prior to FDG
• Parysow O et al. Clin Nucl Med 2007 (Argentina)
• Soderlund V et al. Eur J Nucl Med Mol Imaging
  2007 (Sweden)

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BAT Reduction of FDG Uptake with Warm Temperature

• Uptake incidence of 13.7 during January through
  March and 4.1, during the rest of the year.
• Warm clothing, avoidance of exposure to cold air
  during transit to PET facility,
  temperature-controlled room (75 F) reduces BAT
  FDG uptake significantly
• Warm temperature reduces FDG uptake in BAT
  despite no effect by benzodiazepine
• Cohade C et al. J Nucl Med 2003 (Johns Hopkins)
• Garcia CA et al. Mol Imaging Biol 2006
  (Washington DC)
• Garcia CA et al. Mol Imaging Biol 2004
  (Washington DC)

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BAT Reduction of FDG Uptake with Warm
Temperature Garcia CA et al. Mol Imaging Biol
2006

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BAT and FDG Uptake Summary

• Non-shivering thermogenesis
• Function of age, sex, ambient temperature,
  sympathetic nervous system
• Supraclavicular, Axillae, Neck, Mediastinum,
  Paravertebral, Para-aortic, Parahepatic,
  Paracolic, Suprarenal, Perinephric
• Avoid nicotine and sympathetic NS stimulatory
  agents
• Can be reduced with warm temperature and
  pharmacologically
• Warm clothing, avoidance of exposure to cold,
  temperature-controlled room (75 F)
• Propranolol (20 mg orally one hour prior to FDG)