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
Los Angeles, California
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)
BAT: Structure and Function
Brown Fat
White Fat
BAT: Structure and Function
Hematoxylin-Eosin
Hematoxylin & anti-UCP-1 Ab
Tatsumi M et al. J Nucl Med 45:1189-93, 2004.
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/paravertebral uptake
 Neck (2.3%) > Paravertebral (1.4%) > Mediastinum (0.9%) >
Perinephric (0.8%), overall (up to 4%)
 females > males; children > adults (15% vs. 2%) (p<0.01)
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.
Brown Adipose Tissue
Brown Adipose Tissue
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)
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 (p=0.004)
 Low dose diazepam no effect (p=0.98)
 Medium dose diazepam indeterminate
 Lower FDG uptake in age<10 y compared to age>10 y (p=0.02)
baseline
after fentanyl
BAT: Effect of b-adrenergic agonists
on 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
 Nicotine
 Nicotine + Ephedrine
 Caffeine
3.7x
7.9x
12.0x
slight (p=ns)
 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)
BAT: Effect of b-adrenergic antagonists
on 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 (p<0.0001)
 Pre-propranolol
 Post-propranolol
5.52+/-2.30
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)
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)
BAT: Reduction of FDG Uptake with
Warm Temperature Garcia CA et al. Mol Imaging Biol 2006
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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