Elsewhere, studies being conducted at Imaging Endpoints are focused on facilitating effective clinical trial design, based on the bidirectional translational approach involving clinician feedback and preclinical response, said Ronald L. Korn, M.D., Ph.D., the firm’s founder and CEO.
Dr. Korn said that despite successful preclinical studies, drugs often show dose-related toxicity. He referred to his experience studying vascular disrupting drugs, which were effective in patients with metastasis, but still showed potentially damaging effects on red blood cells.
“We then found the most appropriate preclinical model to test the hypothesis— an MRI using a special contrast agent that measures oxidation, to screen the preclinical agent, which showed the oxidizing effects of this agent,” he explained.
Dr. Korn also cited his experience with stromal disrupting agents, which were promising in early preclinical testing. “We used MRI perfusion imaging to test its mechanism of action,” he said. Interestingly enough, “we also noticed that PET scans were going cold in preclinical phase, but were more appropriate for human testing,” Dr. Korn added.
Working in collaboration with scientists at TexRAD, Dr. Korn and colleagues at Imaging Endpoints used advanced imaging technology and software to extract information from standard medical images, to observe the heterogeneity and morphology of lesions. Quantifying treatment-related changes through texture analysis helps in the detection and measurement of tumor complexity. The resulting images correlate with the underlying biological processes such as blood flow or hypoxia, as well as tumor microarchitecture.
“Once we know the clinical drivers, we communicate with our preclinical colleagues to identify the drug’s mechanism of action on specific signaling pathways,” Dr. Korn explained. The results also enable linkage with genomic and proteomic data.
Dr. Korn’s team is currently developing noninvasive tests to measure mutational status in lung cancer and using advanced imaging tools to distinguish K-ras from wild-type mutations in colorectal cancer, as well as ER+ from ER- breast cancer.
Imaging has yet to be fully integrated into drug discovery and development, but when applied successfully, it can unearth tremendous insights into the biology and effectiveness of a drug, probing important issues like driver mutations and tumor heterogeneity.