Imaging needs to show at an early stage if a specific treatment is working or if a treatment targeting an alternate cellular pathway would better serve an individual patient.  Umar Mahmood, M.D., Ph.D.

New Modalities, Agents Define Role of Molecular Imaging in Drug Discovery

By developing new imaging modalities and molecularly selective agents, radiologists continue to secure the place of molecular imaging—and, consequently, their own place—in drug discovery and development.

“More and more treatments are molecularly targeted. Imaging needs to show at an early stage if a specific treatment is working or if a treatment targeting an alternate cellular pathway would better serve an individual patient,” said Umar Mahmood, M.D., Ph.D., director of animal imaging at Massachusetts General Hospital’s Center for Molecular Imaging Research (CMIR). CMIR aims to bring molecular imaging agents, including optical, MR and PET agents, from the basic science lab to the clinic. Several agents are already in clinical trials.

Also an assistant professor of radiology at Harvard Medical School, Dr. Mahmood oversees all mouse imaging at CMIR, including two MR units, PET/CT, SPECT/CT, and numerous specialized optical imaging systems. Speaking at a recent meeting of industry, academic and government representatives regarding imaging’s role in drug discovery and development, he maintained that every modality makes a different contribution to molecular imaging research.

RSNA 2006 will feature molecular imaging in a couple areas. The Emerging Technologies refresher course track, which made its debut at RSNA 2005, returns with an eight-course comprehensive look at molecular imaging. In addition, the new Molecular Imaging Zone in the newly redesigned Lakeside Learning Center will offer molecular imaging exhibits and posters as well as other tools and information.

Visualizing Cellular Changes

Molecular imaging provides another useful dimension in imaging by allowing radiologists to visualize some of the cellular changes that drive disease processes before they become apparent anatomically. Information gathered from an imaging target, said Dr. Mahmood, can be applied to the diagnosis and treatment of multiple diseases.
“Many diverse diseases may share the same underlying process,” he explained. “Sometimes you hope to see the processes active, and sometimes you hope to see them dormant. Angiogenesis in a heart with severe coronary artery disease is beneficial, but angiogenesis in a tumor is harmful.”

CMIR has developed a number of diverse agents which may improve screening and diagnosis of—as well as speed therapeutic drug development for—some of the most common diseases including cancer, cardiovascular disease, autoimmune disease and infection, said Dr. Mahmood. Two examples are autoquenched near-infrared fluorescence probes, which may be an impetus for bringing optical molecular imaging to the clinic, and agents such as iron oxide nanoparticles for use with MR.

One example of CMIR’s bench-to-bedside focus involves Type I diabetes. “Using a combination of optical- and MR-detectable agents, we have shown that we can image the inflammation associated with Type I diabetes in mice,” Dr. Mahmood said. “This early detection is important. By the time elevated blood sugar is found, it is relatively late in the disease. At that point the islet cells are mostly destroyed and it may be too late for therapies to change the course of the disease.”

Dr. Mahmood and colleagues are using the iron oxide nanoparticles to noninvasively image the inflammation that occurs in these islets, before the disease is detectable by other noninvasive means. “This has worked so well in mice that we are now in clinical trials to test whether MR imaging can reveal the islet inflammation of the pancreas in people who are at high risk for Type I diabetes before clinical symptoms develop,” he said.

More Training Needed

The role of molecular imaging—and radiologists—in drug discovery and development underscores the need for radiology education programs to offer additional training with tracers and with molecular imaging modalities, said Lawrence H. Schwartz, M.D., director of MR imaging at Memorial Sloan-Kettering Cancer Center in New York City.

 “More emphasis will be needed on the basic sciences,” said Dr. Schwartz, who delivered the RSNA 2005 New Horizons Lecture, “Imaging in Drug Discovery: Emerging Roles and Challenges.” “As radiologists, we have always had to know this area, but the future will require an even better understanding of disease pathways.”

Confocal microscopy of a normal pancreas (left) and a pancreas with insulitis (right). The red area is an islet. An optically labeled magnetic nanoparticle (green) demonstrates increased vascularity and leak around the inflamed islet. (PNAS 2004;101:12634-12639) © 2004 National Academy of Sciences, U.S.A.

More information about the Center for Molecular Imaging Research at Massachusetts General Hospital/Harvard University is available at cmir.mgh.harvard.edu.

Molecular Imaging at RSNA 2006

The Emerging Technologies refresher course track returns at RSNA 2006 with an eight-course comprehensive look at molecular imaging. Registration begins June 19. To register, go to rsna2006.rsna.org and click on the Advance Registration, Housing and Course brochure.

RC117
Molecular Biology for Radiologists
A. Molecular Imaging Introduction and Overview
B. Introduction to Molecular Biology: Overview for Imagers
C. Methods in Molecular Biology

RC217
Target Identification and Bioinformatics
A. Proteins for Imaging: Receptors, Enzymes, and Transporters
B. Informatics for Imaging: General Principles
C. Informatics for Imaging: Genomics and Proteomics

RC317
Probe Design II
A. Sensitivity and Specificity Concerns
B. Development of Radionuclide Imaging Probes
C. MR and Optical Probes for Molecular Imaging

RC417
Imaging Modalities and Instrumentation
A. Nuclear Imaging
B. MR Imaging
C. Optical Imaging

RC517
Molecular-Genetic Imaging
A. Reporter Systems in Molecular Imaging: A Comparative Analysis
B. Imaging of Cellular Networks and Protein-Protein Interaction
C. Molecular-Genetic Imaging in Oncology

RC617
Clinical Translation
A. Current and Near-term Applications of Molecular Imaging Research
B. Training for Molecular Imaging
C. Involving Community Imaging Specialists

RC717
Opportunities from Industry and Government
A. Academic-Industrial Collaborations
B. Funding Opportunities: Imaging in the NIH Roadmap
C. Obtaining Approval for Clinical Use of Molecular Imaging Probes

RC817
In Vivo Cellular Imaging
A. General Considerations: Choice of Method
B. Cardiovascular Applications of Cellular Imaging
C. Neurologic Applications of Cellular Imaging