"Potential Nobel Prize" target remains silent for forty years, how has Chinese nuclear medicine achieved the world's first breakthrough?

Ask AI · How can China’s nuclear medicine drugs overcome the forty-year-old puzzle of integrin targets through innovative strategies?

If a medical discovery not only wins the prestigious “Nobel Prize” but also attracts over 50 global drug developers to follow suit, how compelling must it be? If seasoned multinational pharmaceutical companies have all failed here, how high is the barrier?

This is not a hypothetical but the real situation faced by the integrin αvβ3 target over the past 40 years. Now, a breaker has finally appeared, and it comes from China.

Recently, the National Medical Products Administration (NMPA) approved the listing of the Class 1 radioactive innovative drug Technetium-99m Tc Pexritide Peptide Injection (99mTc-3PRGD2), filed by Foshan RidiO Pharmaceutical Co., Ltd. (a subsidiary controlled by Beijing Gilen Tai Medical Co., Ltd.) through a priority review process. It is mainly used as an auxiliary examination for patients with suspected lung cancer and regional lymph node metastasis.

This product is a radiopharmaceutical conjugate drug (RDC), China’s first independently developed Class 1 innovative nuclear drug, and the world’s first broad-spectrum tumor imaging agent used for SPECT imaging.

Most importantly, this product is the world’s first Class 1 innovative nuclear drug successfully listed with integrin αvβ3 as the target. This progress marks a significant milestone for a “star target” studied for nearly 40 years, crossing the critical gap between basic research and clinical application.

Integrins: The Clinical Transformation Pain of a “Nobel Potential” Target

To understand the significance of this product, one must first understand the pain that integrin αvβ3 has brought to the global pharmaceutical industry.

Integrins are a class of transmembrane receptors on the cell surface, formed by non-covalent binding of α and β subunits, mediating cell adhesion to the extracellular matrix and participating in signal transduction and microenvironment regulation. Currently, 18 α subunits and 8 β subunits are known to form 24 different receptor types, playing key roles in immune response, coagulation, wound healing, and tumor metastasis.

Among the entire integrin family, αvβ3 has become a “star target” due to its special role in tumor biology. This receptor is expressed at very low levels and in limited distribution in normal adult human tissues but shows high expression on the surface of various tumor cells such as glioblastoma, breast cancer, prostate cancer, and melanoma. It plays a key regulatory role in tumor angiogenesis, tumor cell proliferation, invasion, and metastasis by mediating endothelial cell adhesion and migration.

The discovery of integrins began in the 1980s. Scientists Richard O. Hynes, Erkki Ruoslahti, and Timothy A. Springer received the 2022 Lasker Award, known as the “Nobel indicator,” for their foundational contributions in this field, making integrin research widely regarded as having Nobel-worthy scientific value.

Despite the undeniable scientific value of integrin αvβ3, since its first identification in 1986, global drug development efforts targeting this receptor have repeatedly failed. A 2023 review in Pharmacological Research states that at least 15 drugs targeting integrin αvβ3 have entered clinical trials worldwide; including all derivatives and different indications, this number exceeds 50.

A notable example of failure is Merck’s cilengitide. As a dual inhibitor of αvβ3/αvβ5, it was the first integrin inhibitor to reach Phase III clinical trials, with high hopes for treating glioblastoma. However, the Phase III CENTRIC trial in 2013 failed to meet its primary endpoint, leading to the termination of development. Similar projects include AstraZeneca’s MedImmune’s Etaracizumab and Johnson & Johnson’s Intetumumab, both of which failed to reach Phase III due to insufficient efficacy.

These failures mainly stem from poor pharmacokinetics, incomplete target inhibition, and signal pathway compensation, revealing deep-rooted difficulties in developing integrin-targeted drugs: traditional “blockade” strategies may not cope with the complex regulation of integrin signaling, shaking industry confidence in integrin-targeted approaches for a long time.

Breakthrough in R&D: China’s Scientists “Cleverly Surpass”

While multinational giants stumble in “dead ends,” Chinese scientists have chosen a different path. Now, China’s first Class 1 innovative nuclear drug Technetium-99m Tc Pexritide Peptide Injection (99mTc-3PRGD2) has been approved, breaking nearly 40 years of R&D deadlock and igniting new imagination in the global pharmaceutical community regarding integrin αvβ3.

99mTc-3PRGD2 is a radiopharmaceutical conjugate drug (RDC), which connects a targeting probe (RGD peptide) with a radioactive isotope via a linker. The probe recognizes and binds to the αvβ3 target, while the isotope serves as a radiation source for imaging. This design fundamentally changes the drug’s mechanism—rather than inhibiting integrin function or killing cells with high integrin expression, it uses integrin αvβ3 as an “anchor” to deliver radioactivity precisely to tumors for imaging.

This strategy is based on solid molecular design. Professor Wang Fan, founder of Gilen Tai, and his team proposed the “interspacing group modification” theory, introducing a PEG4 flexible linker between two RGD motifs, designing a new RGD dimer. This dimer, through the synergistic effect of two RGD sequences, achieves a binding affinity to integrin αvβ3 at the nanomolar (nM) level, far superior to traditional monomeric RGD peptides, enabling highly selective and strong receptor recognition.

Thanks to its high affinity, the probe requires only a low dose to achieve effective targeting in clinical imaging. Additionally, as a targeting tracer, it binds efficiently without inducing functional conformational changes in integrin or activating or antagonizing signals, thus not interfering with normal physiological regulation mediated by integrins. This “targeting rather than attacking” approach provides a new solution to the nearly 40-year transformation dilemma of integrin αvβ3.

What real benefits can such a clever design bring to patients?

Clinical data show that the recently approved 99mTc-3PRGD2 SPECT not only has no statistical difference from the gold standard 18F-FDG PET/CT in differentiating benign and malignant lung tumors but also has significantly higher specificity and accuracy. It corrects 59% of false-positive lymph node metastasis results from 18F-FDG PET/CT, greatly reducing misdiagnosis of lymph node metastases, and significantly improves diagnostic accuracy, especially for tumor staging and follow-up. Meanwhile, with a simpler preparation process, more accessible SPECT equipment, and lower patient examination costs, it greatly enhances the clinical accessibility of nuclear medicine diagnostics. Given the high expression of αvβ3 in various tumor cells, 99mTc-3PRGD2 SPECT is also expected to expand diagnostic markets in breast cancer, glioma, and other fields.

Industry Capital Support, Breaking into the “Integrated Diagnosis and Treatment” Blue Ocean of Nuclear Medicine

As the world’s first approved integrin αvβ3-targeted drug, the value of 99mTc-3PRGD2 extends beyond diagnostics. Its first-mover advantage also paves the “validation track” for subsequent therapeutic drug development—this is the core of the nuclear medicine “diagnosis and treatment integration” feature.

Nuclear drugs have a unique “diagnosis and treatment integration” advantage: by pairing the same targeting vector with different isotopes, they can realize a closed loop of “diagnostic isotope localization and therapeutic isotope killing.” Diagnostic isotopes precisely locate tumors, while therapeutic isotopes use the same targeting molecule for precise treatment. As the first globally approved integrin αvβ3-targeted drug, the clinical success of 99mTc-3PRGD2 validates the druggability of this target and provides a critical clinical foundation for developing αvβ3-targeted therapeutic nuclear drugs or conjugates.

Recognizing the potential of nuclear medicine “diagnosis and treatment integration,” domestic industry leader Baiyang Pharmaceutical Group early invested as a “matchmaker.” In 2022, Baiyang Group made a strategic investment in Gilen Tai, with its listed subsidiary Baiyang Pharmaceutical (SZ.301015) acquiring commercialization rights for several radiopharmaceuticals developed by Gilen Tai, including 99mTc-3PRGD2 and 99mTc-HP-Ark2.

Pharmaceutical innovation is a long and complex process—long R&D cycles, many steps, high barriers—making it difficult for a single company to complete the entire chain independently. Entrepreneurial scientists face “life-and-death” challenges, with insufficient production resources and lack of professional teams, becoming key bottlenecks in translating results. From project initiation, preclinical research, clinical trials, to registration and approval, each step requires specialized teams; any lapse can lead to failure.

As an industry investor focused on healthcare, Baiyang Group leverages a complete industrial ecosystem and professional innovation incubation to fill the gaps in scientist entrepreneurship. By deploying industry resources and providing comprehensive support, it promotes the transformation of scientific achievements from the lab to clinical practice.

From an industry perspective, Baiyang’s “early investment” logic is clear: on one hand, by leveraging mature commercialization capabilities, quickly bringing the more clinically advantageous and accessible 99mTc-3PRGD2 to patients; on the other hand, recognizing the platform value behind the αvβ3 target—success in diagnostics could unlock larger treatment markets. As the clinical value of the target accelerates validation, the development path for αvβ3-related therapeutic drugs will be shortened, and Baiyang’s early locking of this core asset positions it ahead in this track.

Conclusion

In 2022, when the Lasker Award was given to integrin discoverers, the scientific community again discussed the possibility of a Nobel Prize. However, from target discovery to clinical application, integrin αvβ3 has taken 40 years. The approval of 99mTc-3PRGD2 fills the last gap in translating the integrin αvβ3 target from “laboratory to clinic,” turning fundamental scientific discoveries into patient-benefiting drugs. China’s pharmaceutical innovation will leave a significant mark in the history of this major target’s clinical translation.

From a broader perspective, the success of Professor Wang Fan and his team exemplifies China’s evolution from “follow-up innovation” to pioneering “global firsts,” providing a model of “scientist-led innovation deeply integrated with mature industrial ecosystems”: through comprehensive empowerment by industry players like Baiyang, scientists can cross the “valley of death” in results transformation, turning lab achievements into life-saving medicines.

With ongoing capital support and R&D, further research on αvβ3, expansion into more indications, and long-term validation of the diagnosis-treatment integration model are expected to achieve new breakthroughs. In the vast universe of nuclear medicine, a China-led era of nuclear medicine may just be beginning.