Novel approaches in development of Magnetic Resonance contrast agents and their effective utilization

Contrast Agents/Media are substances that improve the visibility of specific organs, tissues, or blood vessels and help in diagnostic imaging and interventional procedures using modalities such as CT, MRI, and Ultrasound. According to IQ4I analysis, the contrast agent/media global market is expected to grow at high single digit CAGR from 2020 to 2027 to reach $7,033.5 million by 2027.

Magnetic Resonance Imaging (MRI) is one of the most powerful techniques in medical imaging, due to its non-invasiveness and radiation-free nature. Compared with other clinical imaging techniques, MRI presents several advantages associated with image flexibility and high spatial resolution, good contrast in soft tissues, and also the ability to provide information related to blood circulation and blood vessels. The use of magnetic contrast agents has allowed clinical researchers and analysts to significantly increase the sensitivity and specificity of MRI. According to IQ4I analysis, the total number of MRI scans performed is estimated to be 109.5 million in 2020, among them, 32.7 million (29.9%) scans were performed with contrast agents and volume of contrast agents.

The presently available MRI contrast agents are small molecule-based T1-weighted gadolinium-based agents. Due to its short circulation lifetime in the body and the relatively low proton relaxation efficiency substantially limit its widespread application. In recent years, several studies in Japan and the United States have indicated that small amounts of GBCAs accumulate in patients' bodies and brains, in particular after repeated GBCA dosing. Because of this reason, several GBCAs usage was either suspended or limited. For instance, European Medicines Agency banned usage of most of the linear MRI agents. The FDA and other regulatory agencies worldwide have also issued warnings. Along with this, lack of precision, which is a consequence of the non-specificity of MRI contrast agents currently in use and which, among other things, causes false-positive findings, is however hindering more widespread use of MRI.

Thus, there is a gradual shift from small molecule-based contrast agents to “dual-mode” nanoparticle-based contrast agents, which acts on both T1 and T2 relaxation times they also have distinct features like nano-size, achieve maximum recognition, diagnosis with high accuracy, compatibility (non-cytotoxic and biocompatible), stability (chemical and photochemical stable) and metabolism (excretion from the body). Nanoparticles with a magnetic responsive atom such as transition metal ions (Cu2+, Fe2+/Fe3+, Co2+, and Mn2+, lanthanide metal ions (Eu3+, Gd3+, Ho3+, and Dy3+) have emerged as the most promising candidates to be used as contrast agents.

Some of the start-up companies and research institutions are engaged in the development of targeted nanoparticle-based contrast agents which will increase the usage of a new contrast agent in the market in near future. Targeted nanoparticles would change MRI from identifying a region of interest to imaging for specific tumor cells. MRI utility provides additional or alternative development path expanding and further de-risks venture investment. For instance, Spago Nanomedical has developed manganese-based contrast agent SpagoPix (SN132D) cancer-selective MRI contrast agent with extraordinary signal strength and potential to significantly improve cancer diagnostics. In April 2019, SpagoPix entered to phase I clinical trial for first-in-human clinical evaluation of SN132D in Patients with Breast Cancer (SPAGOPIX-01).

Similarly, Imagion Biosystems, Ltd has developed MagSense nanoparticles which have an iron oxide (Fe3O4) core and are known to generate T2 and T2* negative MR contrast at 1.5T or 3T. Unlike existing non-specific MR contrast agents such as gadolinium, MagSense nanoparticles employ a targeting moiety. Currently, the company is undertaking a clinical study that includes an investigation of use as an MR contrast agent. In May 2020, the company entered into a collaboration agreement with Siemens Healthcare Pty Ltd to further explore the utility of Imagion’s MagSense nanoparticles as an MRI contrast agent. The collaboration is to identify optimal MRI scanning protocols for the MagSense HER2 targeted nanoparticles for breast cancer. Also, there is an interesting approach to explore bacterial particles as useful MRI contrast agents. For instance, some microbes are found to have the innate ability to synthesize magnetite to form specific intracellular organelles called magnetosomes and it showed notably higher transverse relaxivity compared to the chemically synthesized Superparamagnetic iron oxide (SPIOs). Thus, all these approaches towards the development of nanoparticle-based contrast agents may replace the small molecule-based MRI contrast agents in the future.

Along with these, there is a growing approach for the utilization of technologies such as artificial intelligence for optimization of dosage of contrast agents to avoid their toxicity issues. AI can significantly reduce the dosage of gadolinium required for MRI and provide a clinically acceptable enhanced image by training the AI model algorithmically to enhance the subtle changes apparent with only 10% of the routine gadolinium dosage. Thus, AI technology may open doors to clinical applications using a minimal dosage of MRI contrast to achieve high-quality images, creating a far more favorable balance between diagnostic value and gadolinium administration risk. All these innovative developments provide immense growth opportunities for the contrast agent market.

Major players in the contrast agents global market are GE Company (GE Healthcare) (U.S.), Bayer Group (Germany), Guerbet (France), Taejoon Pharm Co. Ltd., (South Korea), Beijing Beilu Pharmaceuticals Company Limited (China), Bracco Group (Italy), Fujifilm Holding Corporation (Japan), Sanochemia Pharmazeutika AG (Austria), Dongkook Lifescience (Korea), Lantheus medical imaging (U.S.) and Fujipharma Co. Ltd (Japan).



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