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

本项目第一年合成了9种含4-氟苯丙氨酸[Phe(4F)]的多肽。这些肽通过特异性的寡肽转运体积累到某些肿瘤细胞中。该结果提示含Phe（4F）肽可用于基于正电子发射断层扫描（PET）的癌症诊断。为此，我们必须开发一种简便的方法来制备标记为^<18>F的Phe（4F）。第二年，分别以丝氨酸、谷氨酸和赖氨酸为c端氨基酸的三种含对硼苯丙氨酸（Bpa）肽。这些肽的水溶性是Bpa的300倍，它们在肿瘤细胞中的积累与Bpa相当。结果表明，含双酚a肽可能是硼中子俘获治疗（BNCT）的良好候选者。考虑到双酚a作为极具价值的^<10 b> B载体的必要性，我们开发了一种新颖安全的制备双酚a的方法。Kirihata等人报道的对硼苯丙胺醇（Bpa-ol）也是一种有用的化合物，可作为^<10>B的载体。在本研究中，我们合成了一种双酚a和双酚a-ol之间的杂化化合物，目前正在测量它们在肿瘤细胞中的蓄积和杀伤肿瘤细胞的作用。基于本研究的结果，我们新计划阐明核磁共振成像方法，利用特异性积累到肿瘤细胞中的含Phe（4F）或bpa的肽来诊断癌症。

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.