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Brown Adipose Tissue strategies to reduce FDG uptake

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Hossein Jadvar, MD, PhD, MPH, MBA Associate Professor of Radiology and Biomedical Engineering Director of Radiology Research University of Southern California – PowerPoint PPT presentation

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Title: Brown Adipose Tissue strategies to reduce FDG uptake


1
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

2
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)

3
BAT Structure and Function
  • Brown Fat White Fat

4
BAT Structure and Function
  • Hematoxylin-Eosin
    Hematoxylin anti-UCP-1 Ab
  • Tatsumi M et al. J Nucl Med 451189-93, 2004.

5
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.

6
Brown Adipose Tissue

7
Brown Adipose Tissue

8
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)

9
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

10
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)

11
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)

12
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)

13
BAT Reduction of FDG Uptake with Warm
Temperature Garcia CA et al. Mol Imaging Biol
2006

14
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)
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