Title: Brown Adipose Tissue strategies to reduce FDG uptake
1Brown 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
2BAT 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)
3BAT Structure and Function
4BAT Structure and Function
- Hematoxylin-Eosin
Hematoxylin anti-UCP-1 Ab - Tatsumi M et al. J Nucl Med 451189-93, 2004.
5BAT 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.
6Brown Adipose Tissue
7Brown Adipose Tissue
8BAT 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)
9BAT 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
10BAT 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)
11BAT 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)
12BAT 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)
13BAT Reduction of FDG Uptake with Warm
Temperature Garcia CA et al. Mol Imaging Biol
2006
14BAT 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)