KOBE Institute

RIKEN Center for Molecular
Imaging Science
Advanced molecular imaging techniques developed by the RIKEN Center for Molecular
Imaging Science (CMIS) are paving the way for innovative drug development processes.

Yasuyoshi Watanabe

micro-dose trials and drop unpromising compounds before entering actual clinical phasetrials. Another is to build an interface between
animals and humans,” Watanabe says.
Molecular imaging can also be used todiagnose illnesses such as dementia, cancer,
diabetes and even fatigue. CMIS researchers
are seeking to comprehend the onset of suchsymptoms in our body by imaging diseaserelated biomarker molecules, and pursuing
technological innovation for predictive andpreemptive medicine.
RIKEN researchers have for many years beenat the forefront of molecular imaging research,and their efforts accelerated in 2005 with thelaunch of the national Molecular Imaging
Research Program. The base for the programin Kobe was reorganized as the CMIS in 2008.
Since April 2010, the CMIS has been playing
a central role in the government’s new initiative, the Japan Advanced Molecular Imaging
Program (J-AMP).
In 2010, the CMIS took a place on the boardof the third World Molecular Imaging Congress
in Kyoto. In terms of research, the CMIS hascontinued to unveil impressive achievements
in drug discovery, diagnostics and therapeutic biomarkers. For example, thanks to asite-selective reaction developed by a teamled by Hiroshi Mizuma and Hirotaka Onoe
from the CMIS, molecular imaging of the brain
in living conscious animals is now possible
with minimal impact on their physiologicalcondition (J. Nucl. Med. 51, 1068–1075, 2010).
In a separate study led by the CMIS’s Tadayuki
Takashima, CMIS researchers teamed up withcolleagues from the University of Tokyo to develop a PET probe to observe in living mice thefunctions of multidrug resistance-associatedprotein 2—one of the most important proteins associated with hepatobiliary transport(J. Pharmacol. Exp. Ther. 335, 314–323, 2010).
Watanabe sees a challenging but rewarding
future for the CMIS, which he believes is well
positioned to become the global leader in molecular imaging. More extensive collaboration
with the corporate sector will be an importantdriver of the CMIS’s growth, and already thecenter has seen a rise in the number of joint
projects with the healthcare sector to 45 in2010 from 30 the previous year. “We want tocreate a center where we can test molecules
or compounds in humans quickly and safely,”
Watanabe says. “Clinical institutions cannot afford such tasks. This has become another roleof a basic research center like the CMIS.”

The rapid advance in molecular and genomic
studies has opened a new realm of scientificresearch on humans, but the difficulty in observing samples in natural conditions remains
a major obstacle. “We want to look into how
they behave in the body. That is molecularimaging. Our objective is to elevate ‘life science’ to ‘live science’ in humans,” says Yasuyoshi
Watanabe, director of the RIKEN Center for
Molecular Imaging Science (CMIS).
Molecular imaging refers to methods to visualize and track the dynamic behavior of genes,
proteins and other biological molecules in thebody using sophisticated technologies such as
positron emission tomography (PET). Currently,
less than 10% of compounds pass clinical trials
due partly to the differences in targeted deliverability and pharmacokinetics of drug molecules between humans and small laboratory
animals. PET allows such pharmacokinetics tobe observed directly in humans noninvasively,
providing an extra level of certainty prior to
making the decision to take a drug to clinical
trials. Thes are called ‘micro-dose’ clinical trials,
in which pharmacokinetics can be observed
using less than 1% of the normal dosage, well
below the threshold of side-effect occurrence.
“One thing we are aiming at is to conduct

34 | RIKEN ANNUAL REPORT 2010–2011www.riken.jp