New imaging method tracks cancer treatment efficacy in preclinical studies

Some cancer tumors grow by immunosuppression. They manipulate biological systems in the microenvironment, signaling specific sets of immune cells (cells that wipe out abnormal cells) and stop their action. It is no wonder that immunotherapies designed to reestablish anti-tumor immunity are rapidly becoming the treatment of choice for these cancers.

One natural immunosuppressive molecule that helps cancer tumors is indoleamine-2,3-dioxygenase 1 (IDO1).Because it is widespread Cancer tumor, Skin, breast, colon, lung, and blood, scientists are beginning to see it as a promising therapeutic target: suppress its activity,tumor Immunity should return. However, all efforts to date have failed in Phase 3 clinical trials. At this stage, many people with the disease try the optimal dose to test its true efficacy. Why is there such a promising result in theoretically and in the laboratory failing late-stage clinical trials?

To investigate, a team of researchers led by Dr. Ming-ei Zhang, Dean of the Department of Advanced Nuclear Medicine, National Institute of Quantum Radiology, Japan, attempted positron emission tomography (PET) imaging. Follow IDO1 activity after possible treatment. What they found was a groundbreaking event currently published in the BMJ. Journal for ImmunoTherapy of Cancer..

“Our paper focuses on the PET imaging development cycle, from tracer synthesis and biomarker identification to biomarker validation in mouse models of melanoma treated with various immunotherapy regimens. “I will,” said Dr. Zhang.

Scientists started with Radioactive tracerA radiation-emitting chemical known to bind to IDO1. This can be detected by the machine. After confirming that this radiotracer can reliably reflect the level of IDO1 expression at specific sites in the body, can they also reflect the different treatment outcomes of three combination immunotherapy strategies, each containing an IDO1 inhibitor? I checked.

They administered radiotracers and treatments to mice with cancerous tumors and observed what was happening through whole-body PET imaging. Surprisingly, the uptake of radiotracer into tumors is all, even though one of the treatment strategies was clearly more effective than the other and IDO1 was much more suppressed than the other. The treatment seemed to be the same. However, with this outstanding treatment strategy, the radiotracer signal was applied to an extratumor organ called the mesenteric lymph node. This did not apply to the other two treatment strategies. Further investigation confirmed that the radiotracer was also bound to IDO1 in these lymph nodes. But why is this organ? It’s a study for another study.

In this study, scientists investigated another checkpoint. Did this radiotracer peak and valley in the lymph nodes reflect the greatest tumor suppression and reduced therapeutic efficacy? It was found that radiotracer uptake increased from a few days before the peak, peaked at the peak of therapeutic effect, leveled off until a few days before the decline of treatment began, and disappeared when the tumor recurred.

As a result, scientists have come across an unprecedented new biomarker that can non-invasively monitor IDO1 activity. This is a promising alternative to invasive biopsy procedures.

Dr. Lin Xie, co-author of this paper, further explains the results of this study, stating: Equilibrium from tumor resistance to excretion, depending on immunotherapy intervention. “

Another researcher involved in the study, Dr. Kuan Hu, said: “Our study is a powerful way to visualize a patient’s personalized antitumor response to address possible causes of failure in existing clinical trials and thereby improve treatment. The results of the IDO1 regimen have great potential. Our study also presents a potential precision medical paradigm for non-invasive visualization of each patient’s individual response in combined cancer immunotherapy, in the future. Pave the way for Clinical trial For precision anti-cancer immunotherapy. ”

Provided by National Institutes for Quantum and Radiological Science and Technology