Preliminary study for molecular imaging of Bcl-xL as an anti-apoptotic protein.

对于人脑细胞内凋亡系统的研究，Bcl-xL在凋亡信号级联中起着重要的作用。BH 3 I-2'是一种Bcl-xL抑制剂，与Bcl-xL的BH 3结构域结合。我们尝试合成[18F] FBH_3 I-2 ′，期望它能用于活体组织中Bcl-xL的PET测量。用[18F]三丁基氟化铵（TBAF）对BH_3 I-2 ′的三甲基铵盐进行氟化，并对[18F] FBH_3 I-2 ′在大鼠体内的分布进行了初步研究。使用制备型反相HPLC系统纯化产物。蒸发溶剂后，将残余物溶解于盐水中并通过0.22 μ m无菌过滤器过滤。以[18F] TBAF计，放化产率为50%，放化纯度大于99%。合成（包括纯化和灭菌）的总时间为EOB后60 min。肝脏和肾脏对[18 F] FBH 3 I-2 '的吸收较高，这意味着该示踪剂的代谢和排泄较快。脑摄取量远低于血液。还用正电子平面成像系统（Hamamatsu Photonics）动态研究了[18F] FBH 3 I-2'在荷瘤小鼠中的组织分布。注射后肿瘤区域的摄取随时间增加而增加。这些结果表明[18F] FBH_3 I-2 ′不适合于Bcl-xL的显像。

For studying intracellular apoptotic system in the human brain, It is well known that Bcl-xL plays an important role in apoptosis signal cascade. BH3I-2' was reported to be a Bcl-xL inhibitor, which bound to BH3 domain in Bcl-xL. We attempted to synthesize [18F]FBH3I-2' with expectation that it could be used for measuring Bcl-xL in the living tissue by PET. We carried out the labeling of [18F]FBH3I-2' and a preliminary study of biodistribution in rats.Fluorination of the trimethylammonium sault of BH3I-2' with [18F]trtrabutylammonium fluoride (TBAF). was carried out in DMSO at 130°C for 10 min. The product was purified using a preparative reversed phase HPLC system After evaporation of solvent, the residue was dissolve saline and filtered through a 0.22 □m sterile filter. The radiochemical yield was 50 % based on [18F] TBAF and the radiochemical purity was better than 99 % The over all time of synthesis including purification and sterilization was 60 min after EOB.Tissue distribution of [18F]FBH3I-2' was studied in 4 male Sprague-Dawley rats. Liver and kidney show high uptakes of [18F]FBH3I-2', which should mean fast metabolism and fast excretion of this tracer. Brain uptake was much lower than that in blood. Tissue distribution of [18F]FBH3I-2' was also studied in tumor bearing mice dynamically with Positron planer imaging system (Hamamatsu Photonics). The uptake in tumor region was increasingly higher with time after injection. These results suggest that [18F]FBH3I-2'could not suitale for imaging Bcl-xL It is expected that more permiable derivatives of [18F]FBH3I-2' would be useful for imaging Bcl-xL in the living tissues with PET.