PRESS RELEASE
June 21, 2021
Closer to Cure: New Imaging Method Tracks Cancer Treatment Efficacy inPreclinical Studies
Chiba, Japan - New non-invasive method to track the progress of one highly sought-afteranti-cancer immunotherapy can change research in the field
Several cancers grow through immunosuppression, making immunotherapy a promising
approach to treating cancers. But several approaches against one highly sought-after target
molecule for such treatment have failed in late stage clinical trials. To find out why,scientists will need to study what happens to the target molecule over time once thetreatment is administered. Now, in a game-changer for this field, a team from Japan has
discovered a new PET-imaging-based method to achieve this tracking.
Several cancer tumors grow through immunosuppression; that is, they manipulate biologicalsystems in their microenvironments and signal to a specific set of immune cells—those that clear
out aberrant cells—to must stop acting. It is no wonder that immunotherapy designed to reestablish anti-tumor immunity is rapidly becoming the treatment of choice for these cancers.
One natural immunosuppressive molecule that falls prey to helping cancer tumors is indoleamine2,3-dioxygenase 1 (henceforth, IDO1). Because it is found in a broad range of cancer tumors,including those of the skin, breast, colon, lung, and blood, scientists have begun to see it as apromising therapeutic target: Suppress its activity and anti-tumor immunity should be back. But
all endeavors so far have failed in phase 3 clinical trials—the stage at which a large number ofpeople with the disease try out the optimal dose to test its true efficacy. Why is something so
promising in theory and in the lab fizzling out in late phase clinical trials?
To find out, a team of researchers, led by Dr. Ming-Rong Zhang, Director of the Department ofAdvanced Nuclear Medicine Sciences at the National Institutes for Quantum and Radiological
Science and Technology, Japan, tried positron emission tomography (PET) imaging to track
IDO1 activity after a possible treatment has been administered. What they found is a breakthroughnow published in BMJ’s Journal for ImmunoTherapy of Cancer.
“In our paper, we highlight the development cycle of our PET imaging method, starting fromtracer synthesis and biomarker identification to biomarker validation in a mouse model ofmelanoma treated with different immunotherapy regimens,” says Dr. Zhang.
The team of scientists began with a radiotracer—chemicals that emit radiation which can then bedetected by machines—that is known to bind to IDO1. After establishing that this radiotracer canreliably reflect levels of IDO1 expression at specific sites in the body, they proceeded to find out
whether it can also reflect the varied treatment outcomes of three combinatory immunotherapy
strategies, each involving an IDO1 inhibitor.
They administered the radiotracer and the therapies to mice with a cancerous tumor and watched1what happened over time through whole-body PET imaging. To their surprise, despite one of thetreatment strategies clearly having greater efficacy than the others—wherein, IDO1 was inhibitedmuch more than in the others—the radiotracer uptake in the tumors seemed to be the same acrossall treatments. However, in the case of this standout treatment strategy, the radiotracer signal
beamed in an off-tumor organ called the mesenteric lymph node. This was not the case for theother two treatment strategies. Further probing confirmed that in these lymph nodes as well, theradiotracer bound to IDO1. But why this organ? That is research for another study.
In this study, the scientists went on to explore one more checkpoint: did the peak and trough ofthis radiotracer in the lymph nodes mirror those of maximum tumor inhibition and decline oftreatment effect? Turns out the radiotracer uptake increased from a few days before the peak,
peaked with peak treatment efficacy, plateaued until a few days before treatment decline began,
and fizzled out when the tumor relapsed.
So, the scientists had stumbled upon an unprecedented new biomarker with which IDO1 activity
could be monitored non-invasively, a really promising alternative to the invasive biopsy.
Further explaining the results of the study, Dr. Lin Xie, co-author of the paper says, “Our findings
imply that the IDO1 status in the mesenteric lymph node is an unprecedented surrogate markerof the cancer-immune set point, which is an equilibrium state from tumor tolerance to elimination,
in response to immunotherapeutic intervention.”
Dr. Kuan Hu, another researcher involved in the study, says, “Our study holds great potential asa robust method for visualizing personalized antitumor responses in patients, to address thepossible causes for the failure of the existing clinical trials, thereby improving the therapeutic
outcome of IDO1 regimens. Our research also illustrates a potential precision medicine
paradigm for noninvasive visualization of each patient's individual response in combinatorial
cancer immunotherapy and opens up new avenues for future clinical trials for precision anticancer immunotherapies.”###Research Article“Off-tumor IDO1 target engagements determine the cancer-immune set point and predict
the immunotherapeutic efficacy“
Lin Xie, Kuan Hu, Yanhong Duo, Takashi Shimokawa, Katushi Kumata, Yiding Zhang,Cuiping Jiang, Lulu Zhang, Nobuyuki Nengaki, Hidekatsu Wakizaka, Yihai Cao andMing-Rong Zhang“Journal of ImmunoTherapy of Cancer “: June 20, 2021, DOI:

http://dx.doi.org/10.1136/jitc-2021-002616
About National Institutes for Quantum and Radiological Science and Technology
The National Institutes for Quantum and Radiological Science and Technology (QST) wasestablished in April 2016 to promote quantum science and technology in a comprehensive andintegrated manner. QST’s mission is to raise the level of quantum and radiological sciences
and technologies through its commitment to research and development into quantum science2and technology, the effect of radiation on humans, radiation emergency medicine, and themedical use of radiation. To ensure that research and development delivers significant
academic, social and economic impacts, and to maximize benefits from global innovation, QST
is striving to establish world-leading research and development platforms and explore newfields.
Website: https://www.qst.go.jp/site/qst-english/

About Dr. Ming-Rong Zhang from National Institutes for Quantum and Radiological
Science and Technology, Japan:
Dr. Ming-Rong Zhang currently serves as the Director of the Department of Advanced Nuclear
Medicine Sciences, Institute for Quantum Medical Science at the National Institutes for
Quantum and Radiological Science and Technology. He is an expert in the fields of PET
chemistry and molecular imaging and his expertise is demonstrated in over 300 studies in thesefields, published in reputed international and national journals. Currently, part of his researchendeavors focus on improving the detection of immunosuppressive tumors.

Funding information:
This study was funded by JSPS KAKENHI (Grant Nos. 20H03635), JSPS International Joint
Research Program (Grant No. JPJSBP120207203) and the Initiative for Realizing Diversity in the
Research Environment.
Media contact:
Public Relations Section
Department of Management and Planning, QST
Tel: +81-43-206-3026 Email: info@qst.go.jp

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