Comparison of BMIPP-SPECT/CT to 18FDG-PET/CT for Imaging Brown or Browning Fat in a Preclinical Model

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of ¹⁸FDG-PET/CT and ¹²⁵I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of ¹⁸FDG and ¹²⁵I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUV_mean) for ¹⁸FDG and ¹²⁵I-BMIPP significantly correlated in these depots, although uptake of ¹²⁵I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than ¹⁸FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.     

侧链脂肪酸BMIPP的^125I标记和动物体内分布

在乙醇和水的混合溶液中，通过新生存Ｃｕ催化碘同位素交换反应制得＾１２５Ｉ－ＢＭＩＰＰ，经乙醚提取纯化后，其放射化学纯度〉９５％，制备过程中总放射性得率〉４０％，小白鼠体内分布显示２％左右的注射剂量存在于心肌组织，且长时间保持稳定。     

123I标记侧链脂肪酸BMIPP的研制

采用新生态Ｃｕ（Ｉ）催化碘同位素交换反应制备了＾１２３Ｉ－ＢＭＩＰＰ。经高效液相色谱法分离纯化,产品放射化学纯度＞９５％,放化产率为３０％－４０％,经细菌检验,热原检验证明无菌、无热原。动物体内分布显示心肌摄取＾１２３Ｉ－ＢＭＩＰＰ快速、存留时间长,与周围临近组织的放射性比值高,适合于ＳＰＥＣＴ代谢显像。     

^125I—BMIPP在SD鼠体内的分布以及血流改变对其在心肌中分布的影响

报道了＾１２５标记的１５－（对－碘苯）３－（Ｒ，Ｓ）－甲基－十五烷酸（ＢＭＩＰＰ）在ＳＤ鼠体内的分布以血流改变对其在心肌中分布的影响，结果显示：ＳＤ鼠心肌摄取＾１２５Ｉ－ＢＭＩＰＰ在５ｍｉｎ时为３．８６％ＩＤ／ｇ，且５－６０ｍｉｎ保持稳定，３０ｍｉｎ时心／血，心／肺，心／肝比值分别为１．５６，２．０８和１．６２，而＾１２５Ｉ－ＢＭＩＰＰ在肝脏中的清除则较快，对照组心肌摄取＾１２５Ｉ－ＢＭＩＰＰ及心