Peking University Research Team Develops Disruptive Targeted Covalent Radiopharmaceutical

TapTechNews May 26th news, according to the official WeChat public account of Peking University, the journal Nature recently published the first paper in the field of radionuclide therapy in nearly 50 years, and the research results of this paper were completed by the research team led by Liu Zhibo, a professor at Peking University and a leading scientist in Changping Laboratory.

It is reported that the team successfully developed a targeted covalent radiopharmaceutical (CTR), which is a disruptive technology in nuclear drug design, and has obtained excellent early clinical research data in the diagnosis and treatment of tumors, which is expected to rewrite the clinical diagnosis and treatment guidelines of related diseases.

TapTechNews learned from the relevant introduction that targeted radionuclide therapy (TRT) is a transformative treatment method for dealing with advanced metastatic lesions of cancer. TRT uses a radioligand with high affinity and selectivity for tumor-specific targets to deliver a potent β or α radioactive therapeutic nuclide (with a range of only a few microns to a few millimeters) to the lesion for molecular-level precision radiotherapy. When the same ligand binds to a positron or single-photon radioactive diagnostic nuclide, it can also locate the lesion position and evaluate the treatment effect through the commonly used PET and SPECT imaging techniques in nuclear medicine to achieve diagnosis and treatment integration.

In order to make the effect of this molecular-level precision radiotherapy better, targeted radionuclide therapy needs to face at least the following challenges:

First, to make the radionuclide accurately find the tumor cells (through ligand-target binding), that is, excellent tumor targeting;

Second, to make the radionuclide stay in the tumor cells for a longer time, so that the therapeutic radionuclide can fully kill the tumor cells within the limited decay time;

Third, it is necessary to ensure that the radionuclide in normal organs is metabolized and excreted as soon as possible to reduce the side effects of treatment.

It is reported that it is very difficult to solve these three challenges simultaneously, which is the key to further improving the curative effect of TRT.

Targeted covalent radiopharmaceutical is a new drug form that highly selectively fixes the radioactive ligand to the tumor. This technology enhances the tumor uptake and retention of the radioactive ligand and ensures its low uptake in the blood circulation or healthy tissues, which is expected to overcome the problem that the safety and effectiveness of traditional nuclear drugs cannot be achieved at the same time.

The research team verified the effectiveness of CTR from the molecular, cellular, mouse and patient levels based on modern covalent drug molecular engineering. This new drug form has broken through the bottleneck that the targeted radioligand of fibroblast activation protein (FAP, a pan-cancer target) has insufficient tumor uptake and retention, resulting in poor curative effect, and initially overcome the above challenges.

Targeted covalent radiopharmaceutical (CTR) has achieved three major breakthroughs.

Irreversible and selective covalent connection to the pan-cancer target FAP

CTR-FAPI shows better PET imaging contrast

CTR enhances targeted radionuclide therapy by increasing retention

The research team said that under the guidance of Peking University's one-stop scientific and technological innovation layout of basic research, applied research, and achievement transformation, the team is accelerating the development of targeted covalent radiopharmaceutical into a platform technology to empower conjugated drugs for functional transformation. The researchers have recently used CTR-FAPI to conduct more accurate diagnosis in nearly a hundred patients with medullary thyroid carcinoma to guide surgical treatment and have achieved considerable clinical benefits.

In addition, the team is collaborating with Peking University Cancer Hospital and the Cancer Hospital of the Chinese Academy of Medical Sciences to verify the effect in large cancer types such as lung cancer, breast cancer, prostate cancer, and head and neck cancer. Excellent clinical data have attracted many pharmaceutical companies to seek cooperation.