摘要目的:设计并合成靶向CD36新型放射性示踪剂，并对其稳定性、靶向性进行评估。方法:以CD36靶向抗血管生成肽ABT－510为活性骨架，合成前体化合物BQ01、BQ02和BQ03；采用 68Ga标记前体化合物，制备新型示踪剂 68Ga－BQ01、 68Ga－BQ02和 68Ga－BQ03，并通过放射性高效液相色谱法测定其放化纯。对其放射化学和生物学特性进行系统评估，包括体外稳定性、脂水分配系数、结合亲和力、药代动力学，人胶质母细胞瘤U87MG荷瘤小鼠microPET/CT显像、生物学分布和磷屏自显影实验。采用单因素方差分析比较3种探针的肿瘤/肌肉比值(事后检验采用Tukey法)。 结果:68Ga－BQ01、 68Ga－BQ02和 68Ga－BQ03的放化纯均超过95%，在体外PBS和血清中均稳定性良好；脂水分配系数log P分别为－3.81±0.08、－3.60±0.03和－3.85±0.03，均表现出亲水性；体内血液清除半衰期分别为(25.6±0.3)、(38.2±0.2)和(17.5±0.2)min，清除均较为迅速。 68Ga－BQ01、 68Ga－BQ02和 68Ga－BQ03对U87MG细胞具有较高的结合亲和力，抑制常数 Ki分别为(4.30±0.63)、(3.80±0.24)和(2.61±0.31)nmol/L。荷瘤小鼠microPET/CT显像示， 68Ga－BQ01、 68Ga－BQ02和 68Ga－BQ03均在注射后0.5h有明显的肿瘤摄取，SUV max分别为0.68±0.09、0.70±0.09和0.89±0.05；生物学分布示肿瘤组织摄取分别为(0.35±0.09)、(0.53±0.01)和(0.63±0.06)每克组织百分注射剂量率(%ID/g)， 68Ga－BQ03的肿瘤/肌肉比值显著高于 68Ga－BQ01和 68Ga－BQ02( F＝161.50，均 P<0.001)。 结论:3种靶向CD36的放射性示踪剂稳定性好、亲和力强、肿瘤摄取高，且 68Ga－BQ03显像效果最好，有望用于CD36阳性恶性肿瘤的精准诊断。

abstractsObjective:To construct novel radiotracers targeting CD36 and evaluate their stabilities and targeting specificities.Methods:ABT-510, an anti-angiogenic peptide that bound CD36, served as the active scaffold for the synthesis of precursor molecules BQ01, BQ02 and BQ03. These precursors were subsequently labeled with 68Ga to yield the tracers 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03, whose radiochemical purities were determined by radio-high-performance liquid chromatography. A systematic characteristics of the radiochemical and biological profiles were performed, including in vitro stability, lipid water partition coefficient (log P), target-binding affinity, pharmacokinetic behaviour, microPET/CT imaging on U87MG tumor bearing mice, biodistribution, and phosphor-screen autoradiography. The tumor/muscle ratios of three probes were compared by one-way analysis of variance (post-hoc tests with Tukey method). Results:The radiochemical purities of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were all over 95%, and the radiotracers all remained stable in PBS and serum in vitro. The log P values of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were -3.81±0.08, -3.60±0.03 and -3.85±0.03 respectively, indicating hydrophilicity; and blood clearance half-lives in vivo were (25.6±0.3), (38.2±0.2) and (17.5±0.2) min respectively, demonstrating rapid elimination. 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 displayed high binding affinities toward U87MG cells, with inhibition constants ( Ki) of (4.30±0.63), (3.80±0.24) and (2.61±0.31)nmol/L, respectively. MicroPET/CT demonstrated marked tumor accumulation of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 at 0.5 h after administration in U87MG tumor bearing mice, with SUV max of 0.68±0.09, 0.70±0.09 and 0.89±0.05. Biodistribution results showed the tumor uptakes of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were (0.35±0.09), (0.53±0.01) and (0.63±0.06) percentage activity of injection dose per gram of tissue (%ID/g), respectively. The tumor/muscle ratio of 68Ga-BQ03 was significantly higher than that of 68Ga-BQ01 or 68Ga-BQ02 ( F=161.50, all P<0.001). Conclusions:Three CD36-targeted radiotracers demonstrate good stability, strong binding affinity, and high tumor uptake. Among them, 68Ga-BQ03 shows the best imaging performance and holds promise for the precise diagnosis of CD36-positive malignant tumors.