Specialty area: Molecular & Metabolic Imaging

Speaker’s name: Zheng-Rong Lu, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. zhengrong.lu@case.edu

Highlights: · Clinical potential of MR molecular imaging

· Challenges of clinical translation of MR molecular imaging

· Criteria and strategies of designing clinically translatable targeted MRI contrast agents

· Examples of promising MRI molecular imaging technologies for clinical translation

Title: Clinical Translation of MR Molecular Imaging

Target audience: Researchers in the area of targeted MRI contrast agents and molecular imaging and radiologists and clinicians.

Objectives: To be familiar with the advantages and clinical applications of MR molecular imaging, the path and challenges for clinical translation, factors affecting the clinical translation, design considerations of clinically translatable MR molecular imaging technology, examples and recent progress of promising MR molecular imaging technologies.

MRI is a powerful medical imaging modality and provides high-resolution three-dimensional visualization of anatomical structures of soft tissues in the body. However, contrast enhanced MRI has not been effective for clinical molecular imaging because of its low sensitivity and lack of safe and effective targeted MRI contrast agents. Molecular MRI requires the delivery of a sufficient amount of contrast agents to molecular targets to generate detectable signal enhancement. This presentation will discuss the criteria of clinically translatable targeted MRI contrast agents, gaps between academic research and industrial development, and the challenges as well as regulatory considerations for clinical translation of MR molecular imaging.

Safety and customer acceptance are some of the major concerns for clinical translation of MR molecular imaging technologies. Stability, biodistribution, and complete elimination of Gd(III) chelates are the essential parameters for the safety of targeted Gd(III) based contrast agents for MR molecular imaging. Chelation structure determines the stability of Gd(III) based contrast agents. Generally, macrocyclic chelates have much higher chelation stability than linear chelates. Complete excretion of the contrast agents should be achieved in order to minimize any potential toxic side effects and to increase CNR for molecular MRI. Customer acceptance and cost for development also determine the clinical translation of molecular MRI. Many of MR molecular imaging technologies showing great promises in preclinical stages are unable to proceed into clinical translation because of safety concerns, high cost for translation, and poor customer acceptance. Some of imaging agents for contrast enhanced MRI are pulled out from the market even after the FDA’s approval because of poor customer acceptance.

Design and development of any new MR molecular imaging technology for clinical translation should consider safety and regulatory requirements as well as all of the challenges in order to achieve successful clinical development. Several examples of promising MR molecular imaging technologies are discussed in this presentation.