PET肿瘤显像剂是近年来放射性药物的研究热点之一。目前，18F标记的氨基酸类PET脑肿瘤显像示踪剂的研究主要集中在新型非天然氨基酸类型标记物的研究方面。其中，多种18F标记的非天然氨基酸类物质，如O-(2-[18F]氟乙基)-L-酪氨酸（FET）、O-(3-[18F]氟乙基)-L-酪氨酸（FPT）等作为PET脑肿瘤显像示踪剂，已经被广泛研究应用于脑肿瘤的早期临床诊断、指导治疗和预后判断等方面，成为PET脑肿瘤显像领域中的研究重点。本论文以缬氨酸、苯丙氨酸、蛋氨酸等三种天然氨基酸为原料，首次采用3，5-二硝基苯甲酸和2，4-二硝基苯甲酸修饰天然氨基酸的方法得到四个非天然氨基酸类18F标记前体，通过这两种不同取代位置的双硝基芳香环的去硝基氟化反应的对比研究，成功探索出一种针对该类前体的18F标记方法，合成了酯类和酸类共八个新的19F取代产物（标准样品），并且采用该法对四个前体进行18F标记，得到了酯类和酸类共八个新的18F标记目标产物，取得了较好的放化产率30-40%（比一般文献报道20-30%要高）和很高的放化纯度（﹥99%）。所有合成的新目标产物和重要中间体的结构均通过IR、1HNMR、13CNMR、MS验证，19F取代产物亦有19FNMR确认结构，18F标记产物经Radio-HPLC保留时间鉴定结构。对其中六个18F标记目标产物测定了脂水分配系数，并且采用荷S 180肉瘤小鼠动物模型进行了生物活性评价研究，数据显示2，4-二硝基型缬氨酸酸类18F标记物比其酯类及3，5-二硝基型酯类和酸类具有更优越的、更为集中的肿瘤/脑、肿瘤/血峰值比值，在30min时分别达到13.30、2.32，具有成为PET脑肿瘤显像示踪剂的巨大潜力；2，4-二硝基型苯丙氨酸酸类18F标记物突出的优点就是在肿瘤和脑中具有较大的绝对初始摄取量，分别为1.56%ID/g和0.28%ID/g，并且具有良好的滞留性，而且在正常组织中的清除更快、更彻底，同样在PET脑肿瘤显像方面具有一定的潜在应用价值。数据表明，六个18F标记目标物都具有很大的肿瘤/脑比值的峰值，最小的为5.05（1b），最大的达到了13.30（4b），都能很好的克服18F-FDG/PET在脑肿瘤显像中脑本底吸收太大的缺陷，而且比文献报道的18F-FET的肿瘤/脑的比值（2-3之间）大很多。此外，其在正常组织中都具有非常快的清除速率和非常好的清除效果，初步显示出了作为PET脑肿瘤显像示踪剂的巨大潜在应用性。

At present, research on PET tumor imaging agents is one of the most important field in the development of novel radiopharmaceuticals. As for research on brain tumor PET radiotracers, efforts mainly focus on the design and synthesis of new 18F-labeled nonnatural amino acids. Therefore, many 18F-labeled nonnatural amino acids, such as FET, FPT and so on, have already been successfully synthesized and extensively investigated to be applied for early diagnosis of brain tumor, directions on therapy and prognosis of the tumor, becoming the key point in such research field.Four nonnatural amino acid precursors for 18F-labeling, based on natural amino acids modified by 3, 5-dinitrobenznoic acid or 2, 4-dinitrobenznoic acid, have been synthesized in this paper. And we successfully simulated the fluorination process of all the precursors with the application of the denitrofluorination nucleophilic reaction on such substrates for the first time, as a result of which eight novel 19F-substituted compounds have been synthesized and their corresponding 18F-labeled compounds, with high radiochemical yields and purity, have also been successfully radiolabeled. The structures of all the novel compounds and important intermediates were confirmed by IR、1HNMR、13CNMR、MS. Part fluorescence spectra of the target 19F-substituted compounds were discussed and Radio-HPLC has been applied to identify the structures of the 18F-labeled compounds.In addition, we chose six 18F-labeled target compounds, measured their participation coefficients and carried out biodistribution experiments with each of them in S 180 tumor model. The results denmonstrated that the acid product of 18F-labeled nonnatural “valine” modified by 2, 4-dinitrobenozic acid possesses more excellent and concentrated uptake ratios of tumor-to-brain (13.30) and tumor-to-blood (2.32) at the same time point of 30 min after injection than its corresponding ester or products modified by 3, 5-dinitrobenzonic acid. Besides, the acid product of 18F-labeled nonnatural “phenylalanine” bears one prominent merit that it has much biger initial absolute uptake of radioactivity in tumor (1.56%ID/g) and brain (0.28%ID/g) with fine retention in them and faster elimination rate of radioactivity uptake in normal tissues. Consequently, both of the two nonnatural amino acids can be excellent candidates for imaging brain tumors.Furthermore, all the six 18F-labeled compounds have large uptake ratios of tumor-to-brain (5.05-13.30), redeeming the shortcoming of great brain background uptake of 18F-FDG and demonstrating strong potential to be used as PET tumor imaging agents.