Research and Development Projects Adopted in FY2015

Development of novel technologies for multi-modal imaging and quantification of bioactive pharmaceuticals

Project Leader:Watanabe Yasuyoshi

Director, Division Director, Division of Bio-Function Dynamics Imaging, Center for Life Science Technologies, RIKEN

Watanabe Yasuyoshi

Biopharmaceuticals (Drugs based on biological molecule(s), such as antibody and nucleic acids) show good therapeutic efficacy due to their high selectivity toward particular disease-related targets. Thus, biopharmaceuticals would pave the way for therapy with less physical burden on patients. In order to accelerate development of this ideal medical technology, the distribution and dynamics of biopharmaceuticals need to be visualized and quantitated in living organs of our body. We have been developed diagnostic technology using positron emission tomography (PET). PET is a technology capable of visualizing distribution of a molecule labeled with short-lived radioisotopes, which are generated in medical cyclotron. Whereas PET imaging is a powerful method, combination with other diagnostic technologies, such as computed tomography (CT) imaging, gives more informative data than that obtained only from PET imaging. Thus, obtaining images simultaneously from different modalities provides us accurate information on state of disease for diagnosis.

In this study, we develop a method to combine different diagnostic technologies (modalities). Furthermore, in order to realize "theranostics", a combination of therapy and diagnostics, we aim to modify biopharmaceuticals with different functional molecules that play distinct roles in therapy and diagnosis.

To modify biopharmaceuticals with different functional molecules, new organic chemical reactions are required. In this project, we will develop new chemical reactions that enable multiple modifications of biopharmaceuticals. For this purpose, we will expand a series of chemical reactions that can be performed in biological condition. These chemical reactions are collectively called “click chemistry”. Specifically, we are going to develop platform chemicals that have several organic groups with different reactivity toward “clickable” functional molecules.

Installation of functional molecules for therapy to the platform chemicals improves performance of biopharmaceuticals. For example, antibody against breast cancer cell has been modified with anti-cancer drug. This antibody-drug conjugate has been approved to treat inoperable or recurrent breast cancer, and the good results were reported. Thus, antibody-drug conjugate is one of the next-generation drugs. The multiple chemical modification technology in this study would provide innovative strategy for development of antibody-drug conjugate with multiple functional molecules, such as anti-cancer drug, radioisotopes for imaging and therapy, and hydrophilic polymer for improvement of in vivo drug disposition.

Now, we are developing the platform chemicals and functional molecules for click chemistry. Using these small molecules, we will establish a method for multiple chemical modifications of biopharmaceuticals for multi-modal imaging.


Multiple modifications of biopharmaceuticals with different functional molecules provide us innovative strategies for diagnosis and therapy.


Click reaction between azide and alkyne molecules gives a cycloadduct of these molecules.