Zhejiang University to Transfer Two Patents for Novel Gadolinium-Free T1 MRI Contrast Agents at RMB 400,000

Recently, Zhejiang University publicly announced the transfer of two core invention patents, proposing toTwo Patents for MRI Contrast AgentsTransferred through the listing-based pricing method, with a total transfer price of400,000 yuan. According to the information in the patent specifications, the two patents may represent intellectual property arrangements for the same core technology in different countries and regions. The core value of this patented achievement lies in breaking through the technical limitations of traditional magnetic resonance contrast agents, and the preparedGadolinium-Free T1 Imaging Contrast AgentCharacterized by extremely low biological toxicity and excellent biocompatibility, it is a key component in the field of diagnostic imaging.Technical Breakthroughs.The inventor of the patent isSun Jihong and her team。

Magnetic Resonance Imaging (MRI) is based on the principle of nuclear magnetic resonance. It detects electromagnetic signals within the body by applying external high-frequency gradient magnetic fields, thereby generating images of the internal structures of tissues and organs. Due to its non-invasive nature, high resolution, and ability to clearly depict soft tissue details, MRI has become one of the core diagnostic techniques in clinical practice.

However, the inherent contrast between normal tissue and diseased tissue is low,Over 30%Clinical diagnosis relies on magnetic resonance contrast agents. Their core function is to alter the local magnetic field environment, thereby enhancing the signal difference between target tissues and surrounding tissues. This helps physicians accurately identify the location, extent, and nature of lesions, serving as a key prerequisite for improving the accuracy of MRI diagnosis.

Currently, the mainstream and adjunctively used magnetic resonance contrast agents in clinical practice are primarily divided into two categories:One category is gadolinium ion complexes as the core formulation.(such as commercial agents like Gd-DTPA and Gd-DOTA), as the most widely used T1-weighted imaging contrast agents, they achieve signal enhancement by leveraging the magnetic properties of gadolinium ions;Another category is low-toxicity, non-gadolinium contrast agents used as adjunctive regimens,T2 imaging contrast agents, represented by Feridex (superparamagnetic iron oxide injection), rely on the magnetic effects of iron ions for imaging and are primarily used for the diagnosis of targeted organs such as the liver and spleen.

However, both existing classes of contrast agents suffer from unavoidable clinical drawbacks that severely limit diagnostic efficacy and safety. Among these, the safety risks associated with gadolinium-based contrast agents are particularly prominent. Gadolinium ions (Gd³⁺) can accumulate in the skin and visceral tissues; in patients with impaired renal function, this may trigger nephrogenic systemic fibrosis (NSF), a rare but fatal condition. Furthermore, gadolinium ions can undergo long-term deposition in brain tissue, posing potential long-term health risks.

Furthermore, the clearance half-life of small-molecule gadolinium-based contrast agents in blood and tissues typically does not exceed 30 minutes. Their short retention time makes it difficult to meet clinical requirements for prolonged imaging and dynamic monitoring, thereby compromising the diagnostic accuracy for complex lesions.

In contrast, traditional iron-based T2 imaging contrast agents face technical limitations. The hypointense signals they generate are difficult to distinguish from naturally hypointense substances such as endogenous gases, cortical bone, and physiological iron deposits, which can easily lead to misdiagnosis or missed diagnosis. Furthermore, constrained by the phagocytic mechanism of the reticuloendothelial system, T2 imaging contrast agents can only target specific organs such as the liver and spleen, failing to meet diverse clinical needs including angiography and whole-body tissue and organ imaging.

Meanwhile, surface modification of iron oxide nanoparticles is required to improve biocompatibility and prolong circulation time. This process is complex, time-consuming, and costly, which hinders large-scale application. Furthermore, as the practicality of T2-weighted imaging has gradually been phased out in clinical practice, these agents lack the core competitiveness needed to replace gadolinium-based contrast agents.

The team has precisely targeted the numerous pain points of existing magnetic resonance contrast agents and achieved accurate and comprehensive solutions.

First, it comprehensively circumvents the key safety hazards associated with traditional gadolinium-based contrast agents, eliminating the risk of nephrogenic systemic fibrosis (NSF) potentially induced by gadolinium ions (Gd³⁺) as well as the issue of their long-term deposition in brain tissue, thereby fundamentally resolving the toxicity concerns related to gadolinium agents.

Secondly, it addresses the limitation of commercial gadolinium-based contrast agents, which have a short in vivo circulation time (typically less than 60 minutes), thereby meeting the clinical need for prolonged imaging monitoring. Meanwhile, it mitigates the issue where the low signal intensity of traditional iron-based T2 contrast agents is easily confused with endogenous hypointense substances; by employing a T1-weighted imaging mode, it enhances signal distinguishability and reduces the likelihood of misdiagnosis and missed diagnosis.

Furthermore, this technology overcomes the limitations of traditional iron-based contrast agents, which are restricted by the reticuloendothelial system and can only target the liver and spleen for imaging. It expands application scenarios to include angiography and whole-body tissue and organ imaging, thereby accommodating more diverse clinical diagnostic needs.

Meanwhile, it also circumvents the drawbacks of traditional iron-based contrast agents that require complex surface modifications, adopting a simple and feasible preparation process that lowers the barrier to production operations.

In terms of core innovation, this technology has built a differentiated technical system by virtue of its multi-dimensional design breakthroughs. ItPioneered the “polydopamine (3,4-dihydroxy-L-phenylalanine)–ferric ion” chelation system,withBiodegradable Polydopamine Amino AcidsAs the core carrier, it replaces traditional gadolinium ions to serve as the imaging core. This approach completely eliminates the toxicity risks associated with gadolinium-based agents while preserving the advantages of T1-weighted imaging.

This technology constructsAmphiphilic Polymer Nanomicelle Carriers。Hydrophilic BlockBiocompatible materials such as polysarcosine and polyethylene glycol (with a chain length of 1–1,500, preferably 5–200) are selected,Hydrophobic BlockPolydopamine amino acids (with a chain length of 1–500, preferably 5–50) form structures with an average particle size of 20–200 nm, balancing material dispersibility and stability.

It overcomes the technical limitations of traditional iron-based contrast agents, which are only suitable for T2-weighted imaging, successfully enabling their application in T1-weighted imaging while simultaneously meeting the imaging requirements for targeted, vascular, and whole-body scenarios.

Furthermore, this technology employs poly(amino acid)-based biodegradable materials to match“Polymer Synthesis - Iron Ion Complexation - Solvent Exchange”A three-step core preparation process, eliminating the need for complex modification steps, achieves an efficient balance between performance and preparative feasibility.

Leveraging the aforementioned innovative design and technical implementation, this technology demonstrates clear and significant core advantages. It offers enhanced safety assurances; as stated in the patent specification, it exhibits excellent biocompatibility with a cell viability rate of ≥85% within a concentration range of 5–500 μg/mL, and the material is biodegradable. Complete clearance from the body is achieved in approximately 150 minutes in mice, eliminating the risk of tissue accumulation. Its safety profile is significantly superior to that of traditional gadolinium-based contrast agents.

Notably, in the field of magnetic resonance contrast agents, urgent clinical demands have driven continuous research and development of related technologies both domestically and internationally, resulting in a competitive landscape characterized by the coexistence of marketed products and projects under investigation. The following is an overview of selected domestic and international products:

Gadopentetate Dimeglumine (Gd-DTPA, brand name Magnevist):As the first extracellular gadolinium-based T1 contrast agent widely used in clinical practice, it leverages the paramagnetism of gadolinium ions (Gd³⁺) to significantly shorten the longitudinal relaxation time (T1) of tissues, thereby enhancing signal contrast between lesions and normal tissue. This characteristic overcomes the limitations of traditional non-contrast MRI, which has a lower detection rate for soft tissue lesions (such as brain tumors, cerebral vascular abnormalities, and abdominal parenchymal organ lesions), and meets the clinical need for basic whole-body, multi-site contrast-enhanced MRI.

byAcademician Liu Xiaogang, National University of Singapore、Academician Zheng Hairong, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesThe team jointly developedLanND-Gd Protein Complex Contrast Agent.This product is designed to introduce a single N108D point mutation into the lanmodulin (LanM) protein, increasing the number of Gd³⁺ binding sites from one to four, thereby significantly enhancing binding affinity and stability. This contrast agent addresses the limitations of traditional gadolinium-based agents, including short effective imaging windows (<60 minutes), insufficient resolution for fine structures such as cerebral blood vessels, and toxicity caused by in vivo retention. It is suitable for the diagnosis of cerebrovascular diseases (e.g., microvascular malformations) and long-term monitoring of renal function.

ByPei Renjun’s Team at the Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesR&DLESPH Time-Resolved Dual-Signal Switching Contrast Agent, addressing the issues of traditional responsive probes being susceptible to interference from endogenous artifacts (fat, calcification, air) and low accuracy in tumor diagnosis, through“Dual-Signal Cross-Validation”Eliminate artifacts and improve diagnostic accuracy for tumors, particularly those in complex anatomical regions.

ByTeam from the Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of SciencesR&D19F MRI-FLI Dual-Modal Contrast AgentBased on a fluorinated tetraphenylethylene rotaxane structure, this agent integrates 144 magnetically equivalent fluorine atoms to construct an ultra-strong 19F signal source. By leveraging the aggregation-induced emission (AIE) effect and pH-responsive “wheel-axle” interlocking interactions, it narrows the sensitivity gap between 19F MRI and fluorescence imaging (FLI), elevating 19F MRI sensitivity to the micromolar level. This contrast agent addresses the challenges of 19F MRI having significantly lower sensitivity than FLI (a difference of over 1,000-fold) and the inability to achieve synergistic “deep-tissue quantitative imaging + high-sensitivity superficial cellular imaging.” It is suitable for tumor mechanism research, drug tracking, and therapeutic efficacy monitoring.