Drug / Contrast Agent Discovery, Imaging Modalities and Kinetic Analysis

  • Course Type: Graduate Course
  • Semester Offered: Spring
Course Number: 
OPTI 522
Units: 
3
Home Dept.: 
BME
Distance Course: 
No
Course Description: 
Current Topics in drug discovery and molecular imaging involve the integration of a series of research modalities. The Pharmaceutical Industry uses these modalities in their developmental and regulatory efforts to attain new indications. As well, the Medical device community is continually developing new techniques to enhance medical imaging for the earliest detection of disease. Furthermore, kinetic ADME studies (absorption, distribution, metabolism, and excretion) are required so as to determine the fate of these agents as an indicator of efficacy and toxicity. The major objective of this team-taught course is to introduce the student to state-of-the-art methods for drug discovery, contrast agent discovery, newer imaging methodologies, how the biodistribution of these agents affects their efficacy and dosing. In addition, all methods will be complemented by lectures discussing clinical applications for all methods described. A description of the topics are provided below: Contrast Agent Discovery: After comparing the characteristics of each molecular imaging modality as an introduction to the course, the properties of contrast agents for each modality will be presented. Applications of imaging methods and contrast agents will then be discussed, including molecular targeting, responsive detection of molecular biomarkers, assessments of flow, perfusion, and permeability. Finally, these concepts will be combined during a discussion of multi-modality imaging. Molecular Imaging: Smart Contrast: The purpose of this section will be to teach how molecular imaging is evolving towards selective/specific detection of target cells or landmarks. The first seminar will review terminology and give examples of contrast agents. How can they become "smart" for molecular targeting, functional imaging and therapy? What are the primary design considerations when making a new agent? Two other seminars will discuss application areas of smart contrast agents and focus on the brain and heart. Seminars will reflect on the role of contrast agents in these application areas and limitations of these agents. What imaging and treatment paradigms are on the horizon? Imaging Applications: This section will provide discussions on the clinical utility of imaging modalities outlining the rationale for utilizing selective imaging applications for particular disease states. This will include MRI, ultrasound, PET, photoacoustic imaging, SPECT. In addition, a brief treatise on the research methodologies (high throughput screening) for identifying molecular imaging agents for these applications will be discussed. Radionuclide Molecular Imaging: These lectures will provide a basic overview of the principles and practice of molecular imaging with radiotracers. After an introduction to the principles of radioactive decay and gamma-ray emission, the lectures will cover the generation and isolation of radioisotopes and the basic techniques of radiochemistry such as labeling reactions and purification. The lectures will then progress into the mechanisms and dynamics of radiopharmaceutical uptake and distribution in the body. Finally, imaging applications using autoradiography, SPECT, and PET will be discussed. Biodistribution Kinetics (Absorbtion, Distribution, Metabolism, and Excretion): In the first lecture we will describe single-compartment models for pharmacokinetics in both graphical and mathematical terms. We will review in detail the mathematical solution to the resulting differential equation, and discuss its implications in terms of time- activity curves. The mathematics needed to understand this discussion are covered in a first year calculus course. In the second lecture we will discuss two-compartment models as a system of two differential equations and discuss their solution using a matrix formulation. Some familiarity with matrices will be helpful here, but not necessary as we will cover the important concepts in the lecture. Examples, with corresponding time-activity curves, will be provided. In the third lecture we will introduce models with N compartments and discuss in general terms the mathematical form that the time-activity curves take and how they are related to the compartmental matrix. For the fourth lecture we will introduce the concept of an identifiable parameter and show, for the 1, 2 and N compartmental models, what the identifiable parameters are when there is access to a single compartment. Finally, in the fifth lecture we will discuss how imaging can be used to increase the number of identifiable parameters and provide some examples that demonstrate this result.
Prerequisite(s): 
All graduate or 4th year undergraduate status in Biomedical Engineering, Chemistry, Cancer Biology, Pharmacology, Optical Sciences, or other Physical or Biological Sciences and a minimum of one year of undergraduate calculus. An understanding of chemical kinetics is desirable.
Instructor(s): 
Russell S. Witte
Instructor(s): 
Lars R. Furenlid
Instructor(s): 
Eric W. Clarkson
External Instructor(s): 
Terry Matsunaga, Evan C. Unger, Maria Altbach, Philip Kuo, Gregory Woodhead
Contact: 
Those interested in enrolling, please contact Dr. Terry Matsunaga at 626-6689 or 982-5688.
Textbooks: 

None

Academic Integrity

According to the Arizona Code of Academic Integrity, “Integrity is expected of every student in all academic work. The guiding principle of academic integrity is that a student’s submitted work must be the student’s own.” Unless otherwise noted by the instructor, work for all assignments in this course must be conducted independently by each student. Co-authored work of any kind is unacceptable. Misappropriation of exams before or after they are given will be considered academics misconduct.

Misconduct of any kind will be prosecuted and may result in any or all of the following:

  • Reduction of grade
  • Failing grade
  • Referral to the Dean of Students for consideration of additional penalty, i.e., notation on a student’s transcript re: academic integrity violation, etc.
Students with Learning Disabilities

If a student is registered with the Disability Resource Center, he/she must submit appropriate documentation to the instructor if he/she is requesting reasonable accommodations.

The information contained in this syllabus may be subject to change with reasonable advance notice, as deemed appropriate by the instructor.