Japanese Researchers Use Microbubbles to Assess Success of Innovative Cancer Treatment
A team of researchers at Nagoya University in Japan has developed a novel method for evaluating the effectiveness of near-infrared photoimmunotherapy (NIR-PIT), an innovative cancer treatment. By utilizing a biomarker based on microbubbles, the researchers were able to identify areas where the therapy had not been fully applied, offering valuable insights to improve NIR-PIT and make it a viable alternative treatment for various types of cancer.
NIR-PIT is a cutting-edge cancer treatment that combines antibodies and near-infrared light to selectively destroy cancer cells while protecting healthy tissues. The process involves targeting cancer cell proteins with antibodies, which leads to the creation of a light-absorbing substance called IR700. When exposed to near-infrared light, IR700 activates and releases energy that effectively destroys cancer cells. NIR-PIT is considered the fifth cancer treatment option, following surgery, radiation, chemotherapy, and cancer immunotherapy. Enhancing the effectiveness of this treatment could have significant implications for cancer patients worldwide.
A major challenge in effectively treating tumors lies in determining the optimal level of light intensity required to destroy abnormal cell growth while minimizing damage to healthy cells. During surgery, it is difficult to ensure uniform irradiation of target cells due to the reflection and scattering of light by host tissue. This raises the necessity for an indicator that can determine the effectiveness of the treatment.
Dr. Kazuhide Sato and his team at Nagoya University Graduate School of Medicine approached this challenge by examining the differences between tumor vessels and host cells. Previous studies have demonstrated that tumor vessels exhibit irregular shapes, gaps between cells, and poor drainage. During NIR-PIT treatment, this poor drainage facilitates the retention of therapeutic nanoparticles within the tumor, resulting in an enhanced permeability and retention (EPR) effect.
In NIR-PIT treatment, the rapid cell death caused by the therapy increases the permeability in tumor vessels. This, in turn, leads to a ‘super EPR effect’ (SUPR), which is 24 times higher than that of other therapies. Assessing the occurrence of the SUPR effect throughout the tumor is crucial in determining the success of the treatment. To address this, the researchers tested whether larger fluorescent nanoparticles, such as Sonazoid microbubbles, could be retained using the increased permeability. Microbubbles provide an effective means of measuring the SUPR effect as they can be easily detected through ultrasound imaging.
We conducted experiments with larger-sized fluorescent particles measuring 2 mm and 5 mm, and observed increased retention with both sizes, noted Dr. Sato. By utilizing ultrasound imaging to track microbubbles, the team developed a groundbreaking biomarker that enables the measurement of the SUPR effect before and after treatment, providing a means to evaluate the effectiveness of NIR-PIT. In simple terms, a higher retention of microbubbles indicates a higher level of anti-tumor effect resulting from NIR-PIT.
Dr. Sato is hopeful that their discovery will significantly improve cancer treatment for patients. By using this new concept, we could confirm and predict the effects of the treatment after NIR light irradiation, he explained. This is especially crucial for patients who receive insufficient treatment, as additional irradiation can be performed in a flexible manner. Since ultrasound imaging equipment is already available in most hospitals, and the microbubble contrast agent used in this study has already been approved, this technology can be easily implemented in clinical practice.
The study conducted by the collaborative research team involved multiple institutions at Nagoya University, including the Graduate School of Medicine, the Institute of Advanced Research, the Graduate School of Engineering, and the Institutes of Innovation for Future Society. The Institute for Quantum Life Science and JST also contributed to the research. The team’s findings were published in the journal EBioMedicine, a publication of The Lancet.
This breakthrough in using microbubbles as a biomarker for evaluating the success of NIR-PIT treatment represents a significant advancement in cancer therapy. With further research and refinement, this innovative approach could pave the way for more effective and targeted treatments for various types of cancer, offering hope to millions of patients around the world.
