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BAT Molecular Imaging with SPECT-CT, PET-CT, PET-MRI and Fluorescence-PET: A Systematic Review of the Literature Data
EP30034
Poster Title: BAT Molecular Imaging with SPECT-CT, PET-CT, PET-MRI and Fluorescence-PET: A Systematic Review of the Literature Data
Submitted on 30 Apr 2019
Author(s): Tarik Z Belhocine, MD., Ph.D *, Albert A Driedger, MD., Ph.D **, Jean-Luc Urbain, MD., Ph.D ***
Affiliations: * Biomedical Imaging Research Centre (BIRC) – Western University – London, Ontario, Canada ** Emeritus Professor – Western University – London, Ontario, Canada *** Department of Radiology/Division of Nuclear Medicine – Wake Forest University – Winston-Salem, NC, USA
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Poster Information
Abstract: Purpose: Brown adipose tissue (BAT), a mitochondria-rich and richly perfused organ, is a major determinant of the body temperature maintenance. The human body thermoregulation is a physiological condition for the non-shivering and uncoupling non-energy dependent production of heat under the sympathetic nervous system (SNS) stimulation. BAT function has also been documented in pathological conditions including metabolic diseases (diabetes mellitus and obesity), cardio-vascular diseases (heart disease and atherosclerosis), endocrine diseases (hyperthyroidism), SNS derived tumors (pheochromocytoma, paraganglioma, neuroblastoma), benign tumor (hibernoma) and cancer (breast cancer, lymphoma), and also in anorexia/cachexia. A systematic review of the literature data was performed on the hybrid imaging of BAT with nuclear medicine molecular probes.

Subjects and Methods: A literature search was performed on Medline/PubMed using the following key-words: “ BAT ”, “ brown adipose tissue ”, “ brown fat ”, “ PET-CT ”, “ SPECT-CT ”, “ PET-MRI ”, “ Fluorescence-PET ”. Only articles on nuclear medicine radiolabeled tracers used in the BAT imaging were included in the systematic review. Articles on alternative molecular imaging techniques using US, CT, MRI, Cerenkov luminescence imaging, fluorescence imaging, Raman spectroscopy imaging, optoacoustic imaging and infrared thermal imaging were excluded from the review.

Results: In nuclear medicine, BAT imaging with PET-CT, SPECT-CT, PET-MRI and fluorescence-PET has been reported in preclinical studies and in clinical studies. Molecular targets for the visualization of BAT included the β3 norepinephrine (NE) receptor and transporter, the adenosine A2a receptor, the GLUT-1/GLUT-4 glucose transporters, the choline transporter, the LAT1 transporter, the FFA substrate, the TG substrate, the PDE10A receptor, the PD-1/PD-L1 receptors, the SSTR 2-3-5 receptors, the OCT3 transporter, the mitochondrial CB1 and TSPO receptors, the mitochondria and transmembrane voltages, and the TAG-72 antigen. BAT radiolabeled probes were reported for the targeting of perfusion (99mTc-MIBI, 99mTc-tetrofosmin, 15O-H2O, 67Ga), glucose metabolism (18FDG), phosphatidylcholine metabolism (18F-fluorocholine), FFA metabolism (18F-FTHA, 123/125I-BMIPP, 11C-palmitate), TG metabolism (18F-BODIPY-TG), oxidative metabolism (11C-acetate), amino acid transport (11C-methionine), oxygen consumption ([15O]O2), sympathetic system/NE receptor (123I-MIBG, 11C-meta-HED, 18F-fluorodopamine), sympathetic system/NE transport (11C-MBR, 11C-TAZA, 11C-Dalene), sympathetic/NE regulation (11C-metformin), G-protein pathway (11C-MTSX), somatostatin receptors (68Ga-DOTA-NOC), programed cell death pathway (18F/64Cu-anti-PD-L1-VHHB3, 64Cu-NOTA-PD-1/PD-L1, 64Cu-atezolizumab, 111In-PD-L1, 111In-anti-hPD-L1, 68Ga-WL12), benzodiazepine receptor (11C-PBR28, 64Cu-Dis, 18F-DPA), phosphodiesterase receptor (18F-AQ283,18F-MNI-659), cannabinoid receptor (18F-FMPEP-d2,11C-2), mitochondrial membrane potential ΔΨm (18F-FBnTP) and voltage-gated 2+Na channels (125I-BNZA), and tumor-associated glycoprotein 72 (124I-HuCC49∆CH2).

Conclusion: BAT plays a critical role in the body thermostasis, immunity and metabolism. Molecular hybrid imaging with radiolabeled probes may help for the visualization, characterization and quantification of BAT in pathophysiological conditions. BAT’s various molecular targets may also be imaged for preclinical and clinical research.
Summary: BAT function is the thermostasis or the maintenance of the body temperature through the non-shivering dissipation of heat and the non-energy dependent heat production. BAT function was also documented in diabetes mellitus, obesity, cardio-vascular diseases and thyroid diseases. In our systematic review of the literature data, BAT molecular imaging with a number of radiolabelled molecular probes for various molecular targets has been documented with SPECT/CT, PET/CT, PET/MRI and PET/fluorescence.References:
⦁ Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA. J Nucl Med. 2007 Jul;48(7):1077-83.
⦁ Visualization of brown adipose tissue with 99mTc-methoxyisobutylisonitrile on SPECT/CT. Goetze S, Lavely WC, Ziessman HA, Wahl RL. J Nucl Med. 2008 May;49(5):752-6.
⦁ Visualization of interscapular brown adipose tissue using (99m)Tc-tetrofosmin in pediatric patients. Fukuchi K, Ono Y, Nakahata Y, Okada Y, Hayashida K, Ishida Y. J Nucl Med. 2003 Oct;44(10):1582-5.
⦁ Potential false positive Tc-99m sestamibi parathyroid study due to uptake in brown adipose tissue. Wong KK, Brown RK, Avram AM. Clin Nucl Med. 2008 May;33(5):346-8.
⦁ Combining 123I-metaiodobenzylguanidine SPECT/CT and 18F-FDG PET/CT for the assessment of brown adipose tissue activity in humans during cold exposure. Admiraal WM, Holleman F, Bahler L, Soeters MR,
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