Synthetic Study of Peptides Accumulating into Tumor Cells for the Diagnosis and Treatment of Cancer.

在本项目的第一年，我们合成了9种4-氟苯丙氨酸[Phe(4F)]。这些多肽通过特定的寡肽转运体聚集到某些肿瘤细胞中。这一结果表明，含Phe(4F)的多肽可用于基于正电子发射断层扫描(PET)的癌症诊断。然而，为了这个目的，我们不得不开发一种简便的方法来制备标记Phe(4F)。第二年，我们合成了三种分别以丝氨酸、谷氨酸和赖氨酸为C-末端氨基酸的对硼苯丙氨酸(BPA)多肽。这些多肽在水中的溶解度是双酚A的300倍，它们在肿瘤细胞中的积累量与双酚A相当。这些结果表明，含BPA的多肽可能是肿瘤的硼中子俘获治疗的良好候选者。从BPA作为非常有价值的载体的必要性出发，我们开发了一种新的、安全的制备BPA的方法。Kirihata等人报道的对硼苯丙氨醇(BPA-ol)也是一种有用的化合物。在本研究中，我们合成了BPA和BPA-ol的杂化化合物，目前正在进行它们在肿瘤细胞中的积聚和对肿瘤细胞的杀伤作用的测量。作为目前研究的结果，我们新计划阐明利用Phe(4F)-或BPA-多肽特异地积聚到肿瘤细胞中的核磁共振成像方法来诊断癌症。

In the first year of this project, nine kinds of 4-fluorophenylalanine [Phe(4F)] containing peptides were synthesized. These peptides were accumulated into some kinds of tumor cells via specific oligopeptide transporter. This result suggests that Phe(4F)-containing peptides can be utilized for the diagnosis of cancer based on the positron emission tomography (PET). For this purpose, however, we have to newly develop a convenient method for the preparation of Phe(4F) labeled with ^<18>F.In the second year, three kinds of p-boronophenylalanine (Bpa) containing peptides with serine, glutamic acid and lysine as C-terminal amino acid, respectively. These peptides are 300-fold more soluble in water than Bpa, and their accumulation into tumor cells are comparable to that of Bpa. The results suggest that Bpa-containing peptides may be good candidates for boron neutron capture therapy (BNCT) of cancer. From a viewpoint of necessity of Bpa as very valuable ^<10>B carrier, we developed a novel and secure method to prepare Bpa.p-Boronophenylalaninol (Bpa-ol) reported by Kirihata et al.is also useful compound as a ^<10>B carrier. In the present study, we synthesized a hybrid compound between Bpa and Bpa-ol, and are currently undertaking the measurement of their accumulation into tumor cells as well as their tumor cell killing effect.As a result of present study, we newly planned to elucidate nuclear magnetic resonance imaging method for the diagnosis of cancer using Phe(4F)- or Bpa-containing peptides that accumulate specifically into tumor cells.