Perspectives on Brown Adipose Tissue Imaging: Insights from Preclinical and Clinical Observations from the Last and Current Century

Abstract

Brown adipose tissue (BAT) was first described in the 16th century, but until late last century had mainly been considered a tissue with the function of nonshivering thermogenesis, maintaining body temperature in key organs in newborns who have high body surface areas relative to their weight and thus marked radiative heat loss. BAT was believed to have substantially disappeared by adulthood. Molecular imaging with 18 F-FDG PET and PET combined with CT, as well as imaging with 131 I-metaiodobenzylguanidine (MIBG) beginning late last century have shown BAT to be present and active well into adulthood. This review highlights key aspects of BAT biology, early empiric observations misidentifying BAT, pitfalls in image interpretation, and methods to intentionally reduce BAT uptake, and outlines multiple imaging methods used to identify BAT in vivo. The therapeutic potential of increasing the amount or activity of BAT for weight loss and improvement of glucose and lipid profiles is highlighted as a major opportunity. Molecular imaging can help dissect the physiology of this complex dynamic tissue and offers the potential for addressing challenges separating "active BAT" from "total BAT." Research in BAT has grown extensively, and 18 F-FDG PET is the key imaging procedure against which all other BAT imaging methods must be compared. Given the multiple functions of BAT, it is reasonable to consider it a previously unrecognized endocrine tissue and thus an appropriate topic for review in this supplement to The Journal of Nuclear Medicine.

Sympathetic innervation of the supraclavicular brown adipose tissue: A detailed anatomical study

“…With emerging interest in BAT [ 23 ], multiple questions have been asked about its distribution [ 24 , 25 ], the reliability of methods to measure its volume and activity [ 2 , 5 , 26 , 27 ], the role and quantification of beige adipose tissue [ 28 ], its relationship with obesity [ 29 ], its endocrine function [ 3 ], and its innervation [ 19 ]. Clarifying these issues is fundamental in reaching the final clinical goal which would be selective regulation of its activity either using chemical, mechanical, electrical, or thermal therapeutic approaches to control metabolic disorders [ 30 ].…”

Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity

“…Obese individuals with or without type 2 diabetes, who are candidates for GLP-1RA treatment and greatly benefit from such therapy, are prone to insulin resistance, which significantly hampers 18 F-FDG uptake and thus makes imaging with 18 F-FDG-PET/CT inconclusive [83,84]. An alternative radiolabeled tracer, [123I]metaiodobenzylguanidine ([123I]MIBG), is a norepinephrine analog routinely used for imaging of tumors of the sympathetic nervous system and reflects sympathetic stimulation and activation of BAT [85,86]. While not affected by insulin resistance, the uptake in the target tissues may be altered by a range of medications.…”

18F-FDG Uptake in Brown Adipose Tissue After Exposure to the Cold: From Possible Pitfall in Early PET Scans to Metabolic Biomarker

“…These developments cast our interest back to the origin by reminding us that the essence of 18 F-FDG PET/CT is not just reporting the presence of uptake in a target lesion: every single PET/CT scan has much more than this to offer, and "signals" are there just to be detected and correctly interpreted. 18 F-FDG uptake in BAT is the perfect example of this scenario (13).…”