Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC) , Beijing, China.
Adipocyte. 2020 Dec;9(1):542-549. doi: 10.1080/21623945.2020.1814546.
Brown adipose tissue (BAT) is important in monitoring energy homeostasis and cancer cachexia. Different from white adipose tissue, BAT is characterized by the presence of a large number of mitochondria in adipocytes. Translocator protein 18 kDa (TSPO), a critical transporter, is expressed in the outer membrane of mitochondria. We speculated that [F]DPA714, a specific TSPO tracer, may monitor BAT activity in tumor-bearing mice in vivo. We first analyzed the radioactive uptake of positron emission tomography (PET) tracers in BAT of CT26 xenograft mice with 18F-fluorodeoxyglucose ([F]FDG) and [F]DPA714. We also studied the BAT uptake of [F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [F]FDG is quite variable among animals, even in mice of the same tumor model (%ID/g-mean: mean ± SDM, 8.61 ± 8.90, n = 16). Contrarily, [F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [F]DPA714 in BAT was significantly higher on day 26 than that on day 7 in CT26 xenograft model. Taken together, these results strongly indicate the potential feasibility of [F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.
棕色脂肪组织(BAT)在监测能量平衡和癌症恶病质方面很重要。与白色脂肪组织不同,BAT 的特征是脂肪细胞中有大量的线粒体。移位蛋白 18kDa(TSPO)是一种关键的转运蛋白,表达在线粒体的外膜上。我们推测,[F]DPA714,一种特定的 TSPO 示踪剂,可能可以在体内监测荷瘤小鼠的 BAT 活性。我们首先分析了正电子发射断层扫描(PET)示踪剂[F]FDG 和 [F]DPA714 在 CT26 异种移植小鼠 BAT 中的放射性摄取。我们还研究了 [F]DPA714 在 CT26、A549 和 LLC 肿瘤模型中的 BAT 摄取。[F]FDG 的动态分布在动物之间差异很大,即使在同一肿瘤模型的小鼠中也是如此(%ID/g-mean:平均值±SDM,8.61±8.90,n=16)。相反,[F]DPA714 在不同的肿瘤模型和同一模型的不同动物中产生了高质量且稳定的 BAT 成像。有趣的是,在 CT26 异种移植模型中,[F]DPA714 在 BAT 中的%ID/g-mean 在第 26 天明显高于第 7 天。综上所述,这些结果强烈表明 [F]DPA714 PET 成像在研究临床前和临床研究中肿瘤进展过程中的 BAT 和能量代谢方面具有潜在的可行性。