The team of Prof. Chen Xiaoyuan and Prof. Zhang Jingjing, the National University of Singapore, published a review paper titled “Clinical Translation of Radiotheranostics for Precision Oncology” in the Nature Reviews Bioengineering, DOI: https://doi.org/10.1038/s44222-023-00106-9. This paper comprehensively analyses the increasingly importance of radiotheranostics in position oncology medicine, as well as the global market expansion of radionuclide drugs. In particular, the article details the important breakthrough in clinical translation of the innovative radionuclide 177Lu-LNC1004 injection developed by LNC.
—— Focusing on Radiotheranostics ——
Radiotheranostics is a revolutionary approach to cancer diagnosis and treatment that seamlessly transitions from diagnosis to treatment by connecting different radionuclides to tumor-targeted ligands. Compared with traditional radiotherapy and chemotherapy, it has the characteristics of higher specificity and lower toxicity. Based on the expression of tumor specific targets, a personalized diagnosis and treatment plan can be developed for patients.
This paper introduced the clinical research and application of new radioactive isotopes, targets, and tracers. The exploration of new radioactive isotopes is the base of developing nuclide diagnosis and treatment, and the international focus is progressing from β-emitting to α-emitting radionuclides R&D, such as exploring the application of 225Ac on the basis of 177Lu. The advantage of α-emitting radionuclides is that they have better protection for normal tissues while releasing higher energy and DNA damage to cancer cells. On this basis, other α-emitting radionuclides such as 211At, 213Bi, 149Tb and 212Pb are undergoing preclinical and clinical translational studies. At the same time, with the addition of new radionuclides, the "radionuclide diagnosis and treatment pairs" will also be gradually expanded from the existing "best match"-68Ga and 177Lu to 152Tb (PET) / 155Tb (SPECT) and 161Tb / 149Tb, 64Cu (PET)/67Cu and 203Pb (PET)/212Pb. Besides, in addition to widely studied and clinically applied targets such as prostate specific membrane antigen (PSMA) targeting prostate cancer and somatostatin receptor (SSTR) targeting neuroendocrine tumors, this paper also looks forward to promising targets such as fibroblast activating protein (FAP) expressed in pan-tumor, which is expected to promote the development of this field. This paper also introduces the progress in synthetic chemistry that has promote the development of integrated diagnosis and therapy on radiotheranostics, including the implementation of small molecules to antibodies, linear structures to cyclic/polymeric structures, and the introduction of click chemical reactions and next-generation synthesis methods, which further promoted new design strategies.
—— Radiopharmaceuticals—a Global Hot Research Field ——
The paper emphasizes that the global radiopharmaceutical market is in a golden period of development, and some of the anti-cancer radiopharmaceuticals have been approved and entered the market worldwide, and achieved clinical breakthroughs. The radiotheranostics research is flourishing in Europe and North America, and the Asia Pacific region is also rapidly developing. In this context, Prof. Chen Xiaoyuan’s team and DC PHARMA jointly founded LNC with the aim of promoting the research and production of innovative drugs. Since its establishment in early 2021, LNC has laid a relatively complete radionuclide diagnosis and treatment pipelines, among which fibroblast activating protein (FAP) -related products are particularly eye-catching and at the forefront of the world.
177Lu-LNC1004 injection is a FAP-targeted radionuclide therapeutic drug. It has a relatively less suppressive effect on the bone marrow, which can kill tumor cells in a safer and more effective way, to reduce side effects on the human body. Evans Blue (EB) moiety in LNC1004 can increase the tumor effective uptake, extend the treatment time window, and achieve standard or better treatment effects with a reduced amount of radioactive isotopes.
—— Experience Sharing in the Approval of New Drugs ——
177Lu-LNC1004 injection has been approved by the US FDA (IND 158831) and plans to conduct Phase I clinical trials at the National University Hospital of Singapore. A Pre-IND has been submitted to the Center for Drug Evaluation (CDE), NMPA, and comprehensive feedback has been received. During the clinical translation process of the 177Lu-LNC1004 injection, LNC overcame many challenges, such as addressing potential radiation degradation issues, patients screening, and efficacy testing. After multiple consultations with the CDE, a consensus was reached on imaging biomarkers, radiation dose measurement, and dose exploration protocols, etc. LNC is actively promoting investigator-initiated trial (IITs) and conducting further research on the issues raised by the CED to prepare for the phase II clinical trials.
At the end of the paper, the author looks forward to the enormous potential of the 177Lu-LNC1004 injection in the field of oncology treatment, and hopes to further tap into the potential of radiopharmaceuticals and promote the development of radiotheranostics through joint communication with global partners and research teams, making future cancer management more targeted and effective, and developing more personalized and precision diagnosis and treatment plans for patients, ultimately benefiting more patients worldwide.
