검색 상세

The development of PET tracer using ApoPep-1 derivatives for apoptosis imaging : ApoPep-7

  • 오금록 (서강대학교 일반대학원)

초록/요약

세포사멸을 영상화하면 암 치료과정에서 항암제 처리에 의한 치료효과를 모니터링 할 수 있을 뿐만 아니라, 세포사멸의 과도한 증가와 관련된 퇴행성 뇌신경질환을 조기 진단하거나 심근경색 및 뇌졸중에서 병의 진행 정도를 모니터링 할 수 있다. 이 연구에서는 파지 디스플레이 기술로 개발된 ApoPep-1 펩타이드를 이용하여 세포사멸을 표적하는 새로운 화합물 합성하였다. ApoPep-1 펩타이드의 단점을 보완하여 cyclic-ApoPep-amide 펩타이드를 합성하였다. 그리고 triazolium cyclic-ApoPep-amide 와 2-trimethylammonium cyclic-ApoPep-nicotinamide triflate 두가지 전구체를 합성하고, 플루오린-18 표지반응을 진행하였다. Triazolium cyclic-ApoPep-amide 전구체는 낮은 방사성 수율 뿐만 아니라 부산물이 생성되는 단점을 보였다. 반면에 2-trimethylammonium cyclic-ApoPep-nicotinamide triflate 전구체는 온화한 조건에서 높은 방사성 수율로 표지하였다.

more

초록/요약

Apoptosis-targeting probes have tremendous benefits in medical application due to their high potential in diagnosis of diseases relevant to apoptosis, including cancer, myocardial infarction, and strokes. Moreover, as an imaging probe specific to the apoptotic biomarker, it can provide qualitative and quantitative information of therapeutic progression. Such specificity also can expand their potential to the site-specific drug delivery. However, so far, most state-of-art technologies in apoptosis-targeting probes have limitations such as prolonged clearance issues, requirement of calcium ions in binding to the apoptotic cells, and in vitro modification such as fluorescence labeling which can result in protein instability. In this study, we have synthesized a novel apoptosis-targeting probe. ApoPep-1 is a peptide screened from the phage display technique, and it can specifically interact with apoptotic cells in vitro and in vivo. Our results have revealed that the oxidation of thiol group from cysteine can decrease the purity of compound when the ApoPep-1 is presenting as linear form, therefore we designed the cyclic form of peptide (cyclic-ApoPep-amide) to address the purity issue. Triazolium cyclic-ApoPep-amide precursor was synthesized by the introduction of triazolium salt moiety to the cyclic peptide, and 2-trimethylammonium cyclicApoPep-nicotinamide triflate precursor was synthesized by the introduction of 2-trimethylammonium salt. Triazolium cyclic-ApoPep-amide precursor has resulted in low radiochemical yield and additional anionic byproducts production. On the other hand, 2-trimethylammonium cyclic-ApoPep-nicotinamide triflate precursor has shown higher labeling yield at the mild condition. The result of 2-trimethylammonium cyclic-ApoPep-nicotinamide triflate precursor can be applied to the diagnosis and monitoring of disease prognosis, expanding its potential toward the betterment in understanding of pathological and therapeutic mechanisms.

more
반출 Meta View 목록