A Systems-Level Analysis of Total-Body PET Data Reveals Complex Skeletal Metabolism Networks in vivo

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. In vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems. Karla J. Suchacki, Carlos J. Alcaide-Corral, Samah Nimale, Mark G. Macaskill, Roland H. Stimson, Colin Farquharson, Tom C. Freeman and Adriana A. S. Tavares

如今，骨骼除调节矿物质代谢外，还被视为多种代谢过程的关键调控因子。然而，我们对系统层面复杂骨代谢相互作用的理解仍处于初级阶段。体外（in vitro）分子生物学与生物信息学方法常被用于在细胞层面解析疾病相关的机制变化，但这些方法缺乏在体内（in vivo）探究动态多骨代谢相互作用的能力。在此，我们提出一种新颖的整合方法，通过对小鼠18F-FDG扫描进行全身正电子发射断层扫描（PET）网络分析——将其作为骨骼糖代谢的生物标志物——以解析体内复杂的骨代谢相互作用。本研究显示，骨骼内不同骨组织具有独特的糖代谢特征，并形成复杂的代谢网络，而这种网络无法通过单一组织的简单PET标准摄取值分析识别。由于PET放射性示踪剂的多样性及临床全身PET系统的问世，我们的方法应用有望揭示骨骼代谢之外新的生理与病理组织相互作用。

Karla J. Suchacki, Carlos J. Alcaide-Corral, Samah Nimale, Mark G. Macaskill, Roland H. Stimson, Colin Farquharson, Tom C. Freeman and Adriana A. S. Tavares