Positron Emission Tomography (PET) and its Application in Drug Development

Transcription

1 Positron Emission Tomography (PET) and its Application in Drug Development March 20 March 21, 2000 This ten-hour live satellite short course is produced by the Society for Nuclear Imaging in Drug Development (SNIDD) in association with Lehigh Educational Satellite Network (LESN) This course is designed for scientists, physicians, clinicians, and managers in the pharmaceutical and biotechnology industries, in academia, and regulatory agencies who wish to learn more about nuclear imaging technology and methods, and their possible application to the drug design, discovery and approval process. The course will feature internationally-recognized experts from Harvard Medical School, Lawrence Berkeley National Laboratory, Aventis Pharmaceuticals, Sanofi-Synthelabo, National Institutes of Health, Bristol-Myers Squibb Pharmaceutical Research Institute, Merck Research Laboratories, UCLA School of Medicine, Johns Hopkins University, Brookhaven National Laboratories, and Uppsala University in Sweden.

2 Positron Emission Tomography (PET) and its Application in Drug Development Overview This two day course is designed to give an overview of how nuclear imaging using positron emission tomography (PET) can be used to provide PK/PD information in vivo, from animal models to human applications. The course starts out with an introductory session on the basics of PET imaging, including presentations on how a PET scanner works, how radiopharmaceuticals are developed and how physiological information is extracted from a time series of PET images. The second session focuses on the preclinical use of PET in animal models, from the mouse through to non-human primate. Presentations highlight the latest PET imaging technology for small animals, the use of PET radiopharmaceuticals specifically for drug development studies, and an example of PET imaging of neuroreceptors in an animal model. The last two sessions present a range of applications relevant to drug development in humans. Presentations include an overview of the important elements in clinical PET studies, the use of radiolabeled drugs, the use of PET to assess receptor occupancy in the brain, drug effects on readily available PET radiopharmaceuticals, therapeutic evaluation of inhaled pharmaceuticals and assessment of drug target interactions by PET, and finally the development of assays for imaging gene expression and monitoring gene therapy by PET. The course is designed for scientists and physicians in the pharmaceutical and biotechnology industries, in academia, and in regulatory agencies, who wish to learn more about PET and its possible applications in drug development. At the end of the course, participants should be able to: describe how PET imaging works discuss the issues involved in synthesizing radiolabeled compounds describe how tracer kinetic models are applied to PET imaging data to extract quantitative information on physiologic processes list the advantages and disadvantages of using PET imaging for preclinical applications list the essential elements in clinical PET imaging studies describe how PET imaging is used to determine PK and PD give examples of the use of PET imaging in drug development discuss the use of PET imaging for therapeutic evaluation list future opportunities and challenges for PET imaging studies in drug development This symposium is organized by the Society for Nuclear Imaging in Drug Development (SNIDD), an all volunteer, educational, non-profit organization which has the goal of increasing the appropriate use of non-invasive nuclear imaging technology as tools in drug research and development.

3 Program Presenters (alphabetical): Richard E. Carson, Ph.D. is the chief of the Modeling and Physics Section of the PET Department of the National Institutes of Health, Bethesda, MD. For over 20 years, Dr. Carson's research has concentrated on the development and application of tracer kinetic models for new and existing radiotracers for the quantification of in vivo physiological function in humans and primates with PET. Other research interests include image reconstruction algorithms and image processing techniques to improve PET quantification and image quality. Simon R. Cherry, Ph.D. is an Associate Professor in the Department of Molecular and Medical Pharmacology, and Associate Director of the Crump Institute for Biological Imaging at the UCLA School of Medicine. His research interests include in vivo small animal imaging with positron emission tomography (PET), high resolution gamma ray detector technology and development of accurate methods for image reconstruction and image processing of animal PET data. Dr. Cherry is the author of 75 peer-reviewed articles and 10 book chapters related to PET. Jerry M. Collins, Ph.D. is Director of the Laboratory of Clinical Pharmacology at the FDA. He received his Ph.D. in 1976 from the University of Pennsylvania. He spent ten years at the NIH, five of those as Chief of the Pharmacokinetics Section at NCI. He joined the FDA in He has authored or co-authored over 140 papers in the field of clinical pharmacology, primarily emphasizing the applications of PK/PD principles in the field of cancer. His current workis focused upon extending these principles with positron emission tomography. Dr. Collins holds adjunct faculty appointments at Johns Hopkins, Georgetown and the Uniformed Services University. Stephen Dewey, Ph.D. is a Senior Scientist in the Chemistry Department at Brookhaven National Laboratory. His academic appointment is as a Research Professor in the Psychiatry Department at New York University School of Medicine. Dr. Dewey is interested in studying interactions between functionally-linked neurotransmitters using both Positron Emission Tomography and in vivo microdialysis. These studies have been designed to include both the human and non-human primate brain. William C. Eckelman, Ph.D. is Chief of the Positron Emission Tomography Department, National Institutes of Health. Previous appointments include Professor of Radiology at The George Washington University Medical Center ( ) and Vice-President for Diagnostics R&D, The Squibb Institute for Medical Research ( ). Dr. Eckelman has published over 150 journal articles in the field of radiopharmaceutical chemistry and has received several awards including the 1997 Georg de Hevesy Nuclear Pioneer Award of the Society of Nuclear Medicine. He is currently President of The Society for Nuclear Imaging in Drug Development. Alan J. Fischman, M.D., Ph.D. is Associate Professor of Radiology at the Harvard Medical School and Chief of Nuclear Medicine, Massachusetts General Hospital. He received his Ph.D. in Biochemistry from Rockefeller University in Dr. Fischman's research interests include the development of new radiopharmaceuticals; studies of the metabolic alterations that occur in burn patients; development of novel medications for treating cocaine addiction; studies of brain activation in various pathological conditions, and measurements of in vivo pharmacokinetics and pharmacodynamics of therapeutic agents. Richard Frank, M.D., Ph.D. is Senior Director of Clinical Pharmacology, Conventional and Exploratory, for Sanofi- Synthelabo Research Division, with special responsibility for clinical trials throughout Western Europe and North America. Dr. Frank was responsible for one of the earliest collaborations between industry (Zeneca) and academia (Dr. Dean Wong, Johns Hopkins University) for the application of PET to drug development., and he is the outgoing president of The Society for Nuclear Imaging in Drug Development. Dr. Frank was elected to Fellowship in the Faculty of Pharmaceutical Medicine, Royal College of Physicians, London in Sanjiv Sam Gambhir M.D., Ph.D. is an Assistant Professor in the Department of Molecular & Medical Pharmacology at the UCLA School of Medicine. He also directs the bio-imaging assay labs in the Crump Institute for Biological Imaging and is a clinical attending in Nuclear Medicine at UCLA. He has over 15 years experience in PET imaging and over the last 5 years has built a program on molecular imaging with an emphasis on reporter genes and gene therapy.

4 Richard Hargreaves, Ph.D. is Senior Director of Pharmacology and Imaging at Merck Research Laboratories, West Point, PA where he is Worldwide Head of the Task force on Imaging Research. He joined the Department of Pharmacology at Merck Sharp and Dohme's Neurosciene Research Center at Terlings Park in 1988 where the main forcu of his work was on the pharmacodynamics of novel drug candidates on physiological systems. He was in charge of the Headache Research Group and responsible for the development pharmacology of Merck's anti-migraine medication rizatriptan (MAXALT). Dr. Hargreaves was also dirctor of the biology effort for the discovery and development of novel non-peptide substance P (Neurokinin 1) receptor antagonists that are currently in clinical development for prevention of chemotherapy induced emesis and treatment of depression. Donald Heald, Ph.D. is Director of Medical Affairs in the Clinical Pharmacology and Pharmacokinetics for Aventis Pharmaceuticals. Don received his Masters and Ph.D. degrees in Pharmaceutical Sciences from West Virginia University with a concentration in pharmacology and pharmacokinetics. Apart from conducting clinical pharmacology studies in multiple therapeutic areas, his main research interest includes the novel uses of radiotracers in development and theoretical mathematical compartmental modeling of a drug's disposition in the body. Bengt Langstrom, Ph.D. is a Professor of Chemistry at Uppsala University, Sweden and is Director of the Uppsala University PET Center. Dr. Langstrom has over 20 years experience in the synthesis and applications of radiolabeled tracers for PET. He has published over 280 papers in chemistry and another 355 in research related to medicine and the life sciences. He has received several awards for his research, including the 1999 Arrhenius Award from the Swedish Chemical Society. William W. Moses, Ph.D. is Staff Senior Scientist at the Lawrence Berkeley National Laboratory. He received his Ph.D. in Physics from the University of California, Berkeley in His main research interest is the development of instrumentation for Nuclear Medical Imaging, primarily for positron emission tomography (PET). This includes development of: (1) new dense inorganic scintillators for gamma ray detection, (2) novel photodiode array designs for measuring scintillation light, (3) custom integrated circuits containing arrays of low noise charge sensitive amplifiers, (4) new detector designs and scanner geometries incorporating the above elements, and (5) tomographic reconstruction algorithms incorporating the additional information available from these and other novel detector designs Daniel E. Salazar, Ph.D. is Director of Clinical Pharmacology & Experimental Medicine at the Bristol-Myers Squibb Pharmaceutical Research Institute. Dr. Salazar received his Ph.D. from the Department of Pharmaceutics at SUNYAB for his work on elucidating the metabolic and pharmacokinetic mechanisms of increased drug induced toxicity in obesity. He has spent the last 10 years in the pharmaceutical industry first within the Clinical Pharmacology Department at Marion Laboratories in Kansas City, MO and more recently in the Clinical Pharmacology & Experimental Medicine Department at Bristol-Myers Squibb Co, Princeton, NJ. During this time he has directed 60 clinical Phase I/II studies investigating dosage form bioequivalence, drug absorption, first administration to man, pharmacokinetics, pharmacodynamics, disease state interactions, drug-drug interactions and nuclear imaging. Dr. Salazar is the co author of over 30 articles in peer-reviewed journals and in 1995 was named to the editorial board of the Journal of Clinical Pharmacology. Dr. Salazar received the McKeen Cattell Memorial Achievement Award of the American College of Clinical Pharmacology in Henry F. VanBrocklin, Ph.D. is Staff Scientist and Head of Radiopharmaceutical Chemistry at The Center for Functional Imaging, Lawrence Berkeley National Laboratory with an adjunct appointment in the Department of Radiology at UCSF. He received a Ph.D. in Radio-pharmaceutical Chemistry from Washington University in Current research interests include the development of metabolic and receptor-based radiopharmaceuticals for tumor imaging, tracers for adrenergic and NMDA neuroreceptors and I-122 labeled perfusion tracers. Dean F. Wong, M.D., Ph.D. is Professor in the Departments of Radiology and Environmental Health Sciences at Johns Hopkins University. His research focus has been on the development, quantification and application of PET/SPECT neuroreceptor imaging ultimately in human studies of physiology and pathophysiology with special emphasis on neuropsychiatric disorders. His focus has been on the dopaminergic system since the first studies at Johns Hopkins in the early 1980's and since then he has expanded to the serotonergic, glutamate and other neurotransmitter systems to examine hypothesis based research as well as applications for new pharmaceutical drug development and design.

5 Program Agenda Session 1: Introduction to PET Imaging - March 20th, 10:00 a.m. - 12:30 p.m. (EST) 10:00 a.m. Course Introduction and Objectives Richard Frank, M.D., Ph.D. (Sanofi-Synthelabo) 10:30 a.m. PET Imaging Instrumentation William Moses, Ph.D. (Berkeley) 11:10 a.m. Radiopharmaceuticals for PET Imaging Henry VanBrocklin, Ph.D. (Berkeley) 11:50 a.m. Tracer Kinetic Modeling for Quantitative Physiological Imaging with PET Richard Carson, Ph.D. (NIH) Session 2: PET in the Drug Design and Discovery Process - March 20th, 2:00 p.m. - 4:30 p.m. (EST) 2:00 p.m. Session Introduction Richard Frank, M.D., Ph.D. (Sanofi-Synthelabo) 2:10 p.m. High Resolution PET Systems for Small Animal Imaging Simon Cherry, Ph.D. (UCLA) 2:40 p.m. PET Radiopharmaceuticals in Drug Design and Development Bengt Langstrom, Ph.D. (Uppsala) 3:20 p.m. Development of a Novel Strategy for the Treatment of Substance Abuse Stephen Dewey, Ph.D. (Brookhaven) 4:00 p.m. Imaging Substance-P (NK1) Receptors in the Living Brain Richard Hargreaves, Ph.D. (Merck) Session 3: PET in Clinical Development and Drug Approval: I - March 21st, 10:00 a.m. - 12:30 p.m. (EST) 10:00 a.m. Session Introduction Richard Frank, M.D., Ph.D. (Sanofi-Synthelabo) 10:10 a.m. Essential Elements of Clinical Studies Using PET Dan Salazar, Ph.D. (BMS) 10:45 a.m. Clinical PET Imaging of Radiolabeled Drugs Alan Fischman, M.D., Ph.D. (MGH) 11:20 a.m. Receptor Occupancy via Clinical Positron Emission Tomography Dean Wong, M.D., Ph.D (Johns Hopkins) 11:55 a.m. Pharmacologic Stress Tests in Drug Development William Eckelman, Ph.D (NIH) Session 4: PET in Clinical Development and Drug Approval: II - March 21st, 2:00 p.m. - 4:30 p.m. (EST) 2:00 p.m. Session Introduction Richard Frank, M.D., Ph.D. (Sanofi-Synthelabo) 2:10 p.m. Characterization of Inhaled Pharmaceuticals Donald Heald, Ph.D. (Aventis) 2:50 p.m. PET Imaging: Focus upon Drug-Target Interactions Jerry Collins, Ph.D. (FDA) 3:30 p.m. PET Imaging of Gene Expression for Gene Therapy Sam Gambhir, M.D., Ph.D. (UCLA) 4:10 p.m. Closing Remarks Richard Frank, M.D., Ph.D. (Sanofi-Synthelabo) Registration Information LEHIGH EDUCATIONAL SATELLITE NETWORK This program will be broadcast live via KU-band satellite in a compressed digital format. Any site interested in receiving the program but lacking the necesary equipment, may order a video-tape copy of the program. You may also attend the live program on Lehigh's campus. Video tape option is not permitted for individual registration(s). Site license registration allows unlimited viewing access in accordance with the following conditions. Registrations must be received by March 1, Registrations received after that date will be subject to a $50 late registration fee and sites will be charged any additional costs (such as overnight shipping of materials) that result. To register a site, complete the following program registration form and send it to the Lehigh Office of Distance Education (fax submission is accepted). A signature on the form indicates that the signer has read and understood these conditions and is authorized to accept them by his/her company or organization. (Registration Information continued on back.)

6 This program earns 1 CEU (Continuing Education Unit) or is available for 1 Lehigh University graduate credit by admitted graduate students. Each non-credit participant will receive a certification of completion at the end of the course. Please note that Continuing Education Unit (CEU) or non-credit registration is NOT the same as graduate academic credit registration. Only officially admitted and registered graduate students may use the course toward a Lehigh degree, may submit work for evaluation by the instructor, or may earn an official course entry on a Lehigh transcript. Academic host professor: Dr. Ned Heindel, Professor of Chemistry, Lehigh University. Please contact the Office of Distance Education for graduate program admission and registration information. Non-Credit Agreement Organizations wishing to obtain non-credit educational programming provided via live broadcast must register specific reception sites with the University. Each registered site will: Access the program via live satellite transmission or receive one video tape set. For live broadcast: Make and retain one videotape recording of the program to be used for playback only within it's facilities for educational purposes for the duration of the course. The program tape may not be edited, altered, or rebroadcast on any system other than one totally within site facilities. Ensure that the recorded copy of the program tape is not used in any manner without the original and complete copyright notice and credits, duplicated, sold, rented, or provided free to individuals or organizations outside the site facilities. Receive one complete set of print course materials that may be duplicated only for use in conjunction with the legitimate use of the tape copy of the program Register site license program participation by submitting attendance form. Cancel licensing by notifying LESN by March 1, A $50 administration charge will apply to cancellations after that date. Contact Name (This person will receive confirmation and printed materials) Company Address City, State, Zip Work Phone Fax Registration Form Site License Fee: Individual Option (via satellite) : $2,950 $1,025 On-Campus Attendance Option (For those who wish to attend on Lehigh University s Campus): persons at $1,250 = $ persons at $1,125 = $ (2 or more registrants from the same company) (limited seating on Campus, please register early) Videotape Option: $3,200 (Sent 10 days after live broadcast) Payment: Includes one set of printed course materials o Purchase Order enclosed o Please charge my MasterCard, Visa, or American Express. Card Number Expiration Date Authorized Signature Date o Special Needs - I am a person with special physical needs or requirements. My needs are. You may contact me at. A staff member will call you to discuss appropriate arrangements.) Please register at least three weeks prior to the course for special needs/requirements. Please send this form to: Theresa Freeman, Lehigh University, 36 University Drive, Room 216, Bethlehem, PA Contact number: or Fax: For additional information on this course and others offered by Lehigh University, please visit the websites at or For additional information on SNIDD and its programs, please visit the website at