The Design and Testing of a Molecular Imaging Agent: A Case Study of Tc-99m-Galactosyl- Neoglycoalbumin Diagnostic Performance

Date(s):

Location:
Jacobs Hall, Room 2512, Jacobs School of Engineering, 9500 Gilman Dr, La Jolla, San Diego, California 92093

Sponsored By:
Prof. Truong Nguyen

Speaker(s):
David R. Vera, PhD
David R. Vera, PhD

Abstract:

Radiopharmaceuticals, also called molecular imaging agents, if designed properly, can provide cross-sectional images of internal organs. These images can be used by physicians to diagnosis organ function. Modern molecular imaging agents accumulate within an organ by binding to a specific receptor. Consequently, the rate of accumulation is a function of the affinity and number of receptors within the organ. This lecture will present an example of how the chemical properties of a molecular imaging agent, Tc-99m-galactosyl-neoglycoalbumin (TcNGA), was used to optimize its diagnostic performance. The case study begins with the construction of a physiochemical model of liver accumulation, which incorporates the bimolecular interaction of the molecular imaging agent and the receptor within the liver. The model was described by a set of non-linear differential equations containing a second-order chemical reaction (TcNGA-receptor binding) and linear observational couplings (sequential images of heart and liver). A sensitivity analysis was performed to investigate the ability to chemically control the observations. Local identifiability was accessed to determine if sequential heart and liver images could provide estimates of receptor affinity and concentration with adequate precision for a medical diagnosis. Plausibility was assessed (comparison of measured versus model estimates) after performing a set of clinical imaging studies using the optimal chemical properties defined by the local identifiability analysis. Lastly, the diagnostic performance of the model parameters was assessed by receiver-operating characteristic analysis. This design process led to selection of a TcNGA chemical structure of moderate receptor affinity, and the injection into the patient of enough TcNGA molecules that would permit the second-order operation of the radiopharmacokinetic system.


Speaker Bio:
Dr. David R. Vera is Professor of Radiology & of Surgery at U.C. San Diego, and director of the UCSD In Vivo Cancer and Molecular Imaging Program. His research focus is the design of targeted diagnostic agents capable of measuring receptor density and affinity. Dr Vera began his career at U.C. Davis, where he contributed to the development of galactoscint, the first receptor-binding radiopharmaceutical to be approved for human-use. Dr Vera’s current research uses receptor-binding technology for cancer imaging. A new agent, tilmanocept, was developed in collaboration with Drs Anne Wallace and Carl Hoh, and approved by the FDA in 2013 for sentinel lymph node mapping. Currently Dr Vera is developing a fluorescent version of tilmanocept, which will be used during robotic surgery.

Contact:
Jamie Gonzalez (jsgonzalez@eng.ucsd.edu)