Introduction to Drug Evaluation and Dose Estimation
Nanoengineering, energized by the desire to find specific targeting agents, is leading to dramatic acceleration in novel drug design. However, in this flurry of activity, some issues may be overlooked. This is especially true in the area of determining dosage and evaluating the effects of multiple agents designed to target more than one site of metastasis.
Offering the unique perspective of a medical physicist who has worked directly with cancer patients for over three decades, Radiopharmaceuticals: Introduction to Drug Evaluation and Dose Estimation starts by exploring the recent history and current state of the field. Then, citing key research and practical examples, the author looks at how to run studies and employ estimation and evaluation methods that lead to the best multiple agents with the least amount of trial and error. He discusses methods that will allow researchers to more rigorously:
- Differentiate one radiopharmaceutical (RP) from another
- Estimate radiation doses
- Correlate results across various species to realize more informed data from clinical trials
Incorporating developments in nanotechnology and radiology, with the ultimate goal of achieving personalized patient-specific treatment, this book crosses disciplines to addresses a range of topics including:
- Preclinical RP development
- Organization of clinical trials
- Determination of activity in vivo
- Modeling and temporal integration with a look at the mass law for tumor uptake as a function of tumor size (discovered by the author)
- Absorbed dose estimates with and without clinical correlations
- Multiple-modality therapy
Dr. Lawrence Williams has devoted most of his life’s research to tumor detection and treatment, and his discoveries continue to influence evolving therapies. As s a medical physicist, he is eminently qualified to bring unique insight into the discussion of radiopharmaceutical dosage rates and efficacy.
Table of Contents
Tumor Targeting and a Problem of Plenty. Preclinical Development of Radiopharmaceuticals and Planning of Clinical Trials. Selection of Radiopharmaceuticals for Clinical Trials. Absorbed Dose Estimation and Measurement. Determination of Activity In Vivo. Modeling and Temporal Integration. Functions Used to Determine Absorbed Dose Given Activity Integrals. Absorbed Dose Estimates without Clinical Correlations. Dose Estimates and Correlations with Laboratory and Clinical Results. Multiple-Modality Therapy of Tumors. Allometry (Of Mice and Men). Summary of Radiopharm-aceuticals and Dose Estimation. Index.
Lawrence E. Williams, Ph.D., is a professor of radiology and an imaging physicist
at City of Hope National Medical Center in Duarte, California. In addition, he is an
adjunct professor of radiology at University of California–Los Angeles (UCLA).
While in high school, he was one of 40 national winners of the Westinghouse (now
Intel) Science Talent Search. Dr. Williams obtained his B.S. from Carnegie Mellon
University and his M.S. and Ph.D. degrees (both in physics) from the University of
Minnesota, where he was a National Science Foundation (NSF) fellow. His initial
graduate training was in nuclear reactions at Minnesota, where he demonstrated
excited states of the mass-4 system (4He*). He later extended this work by finding
excited levels of mass-3 nuclides while working at the Rutherford High Energy
Laboratory in England. Since obtaining the National Institutes of Health (NIH) support
to become a medical physicist, Dr. Williams has devoted most of his research to
tumor detection and treatment and has written approximately 250 total publications
as well as a number of patents in nuclear imaging and radionuclide therapy. He is a
coauthor of Biophysical Science (Prentice Hall, 1979) and editor of Nuclear Medicine
Physics (CRC Press, 1987). He has been a grant and site reviewer for NIH since the
mid-1990s. Dr. Williams is associate editor of Medical Physics and a reviewer for
several other journals. He is a member of the American Association of Physicists
in Medicine (AAPM), the Society of Nuclear Medicine, the New York Academy of
Sciences, Sigma Xi, Society of Imaging Informatics in Medicine (SIIM), and the
Society of Breast Imaging. Dr. Williams has received a lifetime service award from
the American Board of Radiology.
Among Dr. Williams’ most significant biophysical discoveries is the mass-law
for tumor uptake as a function of tumor size. He was also codiscoverer (with Richard
Proffitt) of tumor targeting with liposomes. This work involved one of the first applications of normal organ blockage by use of an unlabeled agent—that is, a two-step
process. Dr. Williams has developed a pair of indices for quantifying the ability of a
radiopharmaceutical to permit imaging or therapy of lesions in animals or patients. He
has also demonstrated that radioactive decay must be considered inherently as one possible exit route in modeling analysis of radioactive drugs. With his colleagues at City of Hope, Dr. Williams measured and calculated the brake radiation dose result for a source of 90Y in a humanoid phantom. This study remains as one of the few examples of a comparison of dose estimates and measurement in the nuclear medicine literature.
This high-quality hardcover volume is a textbook providing an exposition … on the development and evaluation of antibody-based and other targeted radionuclide therapies … unique in the targeted radionuclide therapy literature.
—Medical Physics, May 2012
The book covers a very important topic and fills a gap not covered by others. I believe that it will be a very valuable in our education of Ph.D. students and also very valuable for researchers in this area. I will recommend the book to my colleagues.
—Professor Sven-Erik Strand, University of Lund
The reader is taken on a journey to discover radiopharmaceutical evaluation and dose estimation. The various chapters cover all aspects of radiopharmaceutical development (tumor targeting, preclinical development, selection of radiopharmaceuticals for clinical trials, etc). Chapters dedicated to dosimetry go beyond the usual discussion to cover aspects more related to pharmacokinetics assessment (modeling and temporal integration). Of particular interest are the chapters dedicated to absorbed dose/effect correlation. This is very relevant, especially since recent publications indicate that, in the context of molecular radiotherapy, if the biological end-point is clearly defined and the dosimetric approach is carried out in a rational way, absorbed dose (or derivates) will correlate with observed toxicity or efficacy.
The book is written in a very clear style, and is accessible not only to physicists, but to any professional involved in radiopharmaceutical development and clinical or preclinical experiments. All chapters end with a summary that recapitulates the important points addressed in the chapter, and this a very helpful feature of this book.
Through 30 years of experience, Prof. Williams shares with us ideas, caveats, and hints applicable to the domain. In the acknowledgements, he indicates his will to ‘put some chips back in the pot.’ This is exactly how I receive this book: