유전자 발현을 활용한 루테튬 (177Lu)의 암 치료 효능 검증
Verification of the Cancer Therapeutic Efficacy of Lutetium-177 Using Gene Expression
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Lutetium (177Lu), with its theranostic properties, is one of the most widely used radioisotopesand has a large share of the radiopharmaceutical market due to its many applications and targetedtherapeutic research using lutetium-based radiopharmaceuticals. However, lutetium-basedradiopharmaceuticals currently approved by the US Food and Drug Administration (FDA) are limited tothe indications of gastrointestinal cancer, pancreatic neuroendocrine cancer and metastatic castrationresistantprostate cancer. To overcome these limitations, we aimed to demonstrate the feasibility ofexpanding the use of lutetium-based radiopharmaceuticals by verifying the availability and therapeuticefficacy of lutetium produced in a research reactor (HANARO). In this study, we confirmed the therapeuticefficacy of lutetium by using cancer cells from different types of cancer. In addition, we selected cancerbiomarkers based on characteristics common to various cancer cells and compared and evaluated thetherapeutic efficacy of lutetium by regulating the expression of target genes. The results showed thatmodulation of cancer biomarker gene expression resulted in higher therapeutic efficacy compared tolutetium alone. In conclusion, this study verified the potential use and therapeutic efficacy of lutetiumbased on the production of a research reactor (HANARO), providing fundamental evidence for thedevelopment of lutetium-based radiopharmaceuticals and the expansion of their indications.
Abstract
Lutetium (177Lu), with its theranostic properties, is one of the most widely used radioisotopesand has a large share of the radiopharmaceutical market due to its many applications and targetedtherapeutic research using lutetium-based radiopharmaceuticals. However, lutetium-basedradiopharmaceuticals currently approved by the US Food and Drug Administration (FDA) are limited tothe indications of gastrointestinal cancer, pancreatic neuroendocrine cancer and metastatic castrationresistantprostate cancer. To overcome these limitations, we aimed to demonstrate the feasibility ofexpanding the use of lutetium-based radiopharmaceuticals by verifying the availability and therapeuticefficacy of lutetium produced in a research reactor (HANARO). In this study, we confirmed the therapeuticefficacy of lutetium by using cancer cells from different types of cancer. In addition, we selected cancerbiomarkers based on characteristics common to various cancer cells and compared and evaluated thetherapeutic efficacy of lutetium by regulating the expression of target genes. The results showed thatmodulation of cancer biomarker gene expression resulted in higher therapeutic efficacy compared tolutetium alone. In conclusion, this study verified the potential use and therapeutic efficacy of lutetiumbased on the production of a research reactor (HANARO), providing fundamental evidence for thedevelopment of lutetium-based radiopharmaceuticals and the expansion of their indications.
참고문헌 (19)
- Maydelid TN, "Nanoradiopharmaceuticals based on alpha emitters : recent developments for medical applications", Pharmaceutics, 13(8), pp.1123~ (2021)[DOI]
- George S, "Radiopharmaceutical therapy in cancer : clinical advances and challenges", Nat. Rev. Drug. Discov, 19, pp.589~608 (2020)[DOI]
- Jiajia Z, "Alpha-emitters and targeted alpha therapy in cancer treatment", iRADIOLOGY, 1, pp.245~261 (2023)[DOI]
- Rafael N, "General concepts in theranostics", PET Clin, 16(3), pp.313~326 (2021)[DOI]
- Jose FGM, "Theranostics in nuclear medicine : Emerging and reemerging integrated imaging and therapies in the era of precision oncology", Radiographic, 40(6), pp.1715~1740 (2020)[DOI]
- Suliman S, "Radiophamaceutical treatments for cancer therapy, radionuclides charateristics, applications, and challenges", Molecules, 27(16), pp.5231~ (2022)[DOI]
- Chiara G, "Radiation resistance : A matter of transcription factor", Front Oncol, 11, pp.662840~ (2021)[DOI]
- Krishnan V, "A regulatory role for RUNX1, RUNX3 in the maintenance of genome integrity", Adv. Exp. Med. Biol, 962, pp.491~510 (2017)[DOI]
- George SC, "Developments in 177Lubased radiopharmaceutical therapy and dosimetry", Font. Chem, 11, pp.1218670~ (2023)[DOI]
- Typhanie L, "Safety and therapeutic optimization of Lutetium-177based radiopharmaceuticals", Pharmaceutics, 15(4), pp.1240~ (2023)[DOI]
- Ute Hennrich, "Lutathera®: The First FDA- and EMA-Approved Radiopharmaceutical for Peptide Receptor Radionuclide Therapy", Pharmaceuticals, 12(3), pp.114~ (2019), MDPI AG[DOI]
- Jaleh F, "FDA approval summary : Lutetium Lu177vipivotide tetraxetant for patients with metastatic castration resistant prostate cancer", Clin. Cancer Res, 29(9), pp.1651~1657 (2023)[DOI]
- Ito Y, "The RUNX3 family : developmental regulators in cancer", Nat. Rev. Cancer, 15, pp.81~95 (2015)[DOI]
- Zhang C, "DGCR8", miR-106 axis enhances radiosensitivity of head and neck squamous cell carcinomas by downregulating RUNX3, 2020, pp.7, 582097~
- Krishnan V, "A regulatory role for RUNX1, RUNX3 in the maintenance of genome integrity", Adv. Exp. Med. Biol, 962, pp.491~510 (2017)[DOI]
- Kim DM, "RUNX3regulates the susceptibility against EGFR-targeted non-small cell lung cancer therapy using 47Sc-conjugated cetuximab", BMC Cancer, 23, pp.652~ (2023)[DOI]
- Delong L, "Cancer biomarkers for targeted therapy", Biomarker Research, 7, pp.25~ (2019)[DOI]
- Lee YS, "RUNX3 inactivation is a crucial early event in the development of lung adenocarcinoma", Cancer Cell, 24(5), pp.603~616 (2013)[DOI]
- Ja-Yeol Lee, "Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence", Cells, 12(20), pp.2438~ (2023), MDPI AG[DOI]