A common theme among the conference's participants is that development of molecular imaging agents should start early in the drug development process. According to Juri Gelovani, M.D., Ph.D., president of the Academy of Molecular Imaging, this should happen as soon as a clinical target is locked in, perhaps even preceding development of the therapeutic itself.
Whether it's measuring target expression levels or levels of receptor occupancy and determining pharmacodynamics or pharmacokinetics, the effects of biological approaches need to be validated in parallel to drug development in order to allow for timely transition into the clinics, concurred Thomas Krucker, head of molecular imaging for the global imaging group at Novartis Institutes for BioMedical Research. Co-development of the drug and diagnostic together would save time and resources.
Molecular imaging should be integrated with the drug discovery project teams, rather than run like a core service. At Novartis, he said, they develop customized solutions that use imaging to seek information that can't be found through other technologies.
Labeled biopharmaceuticals are an obvious source for imaging agents, Krucker said. Yet many biologicals display properties such as slow clearance and low target to background ratios, and because of their large size they may suffer from low stability or poor tissue penetration as well, making them less than ideal for the purpose. These issues can sometimes be addressed by engineering the proteins into smaller formats, for example Fab fragments or diabodies, instead of intact monoclonal antibodies.
Imaging agents, as compared to doses of therapeutic agents, are administered in very low amounts that don't induce pharmacologic effects, added Dr. Gelovani. They should provide quantitative information about the spatial distribution and magnitude of drug-target expression and activity in tumors as well as other normal organs and tissues.