Radiotracers in Drug Development: 1st Edition (Hardback) book cover

Radiotracers in Drug Development

1st Edition

Edited by Graham Lappin, Simon Temple

CRC Press

320 pages | 7 Color Illus. | 105 B/W Illus.

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pub: 2006-04-03
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Although there are numerous books on drug metabolism, Radiotracers in Drug Development is unique in explaining how radiotracers are used to elucidate a drug’s absorption, distribution, metabolism, and excretion (ADME). Covering traditional and recent technologies and applications, the book takes a strong industrial approach, discussing the basics of scintillation counting and untangling the various data processing methods often specific to individual manufacturers.

The chapters include descriptions of the latest micro-plate counters and the growing applications of accelerator mass spectrometry, positron emission tomography, gamma-scintigraphy, and radioluminography. In addition to describing how the analytical technologies work, the contributors explain how the data are interpreted and used in the drug registration process.

A unique reference and training aid essential for every drug metabolism department or drug metabolism research team, the book provides insight into the use and practice of ADME in a way that is both instructive and practical. Moving easily across the boundaries of biology, chemistry, and physics, this is the only comprehensive, interdisciplinary resource covering the how-tos of employing radiotracers in drug development. It provides detailed information on how the science is relevant to the registration process.


“…a well-structured and easily readable book with clear illustrations (a few in colour) and a comprehensive, 10 page, index. It will serve as a good introductory text to students and others who wish to gain a basic understanding of the application of radioisotopes in drug metabolism and disposition studies; I will certainly recommend it to students and new starters in our own department.”

— Andy Gray, AstraZeneca, UK, bts (The British Toxicology Society, Newsletter, Winter 2006, Issue 29

“It is a well planned, laid out, and written tome. The listing of 278 pertinent references and further reading material, together with tables, formulae both chemical and mathematical, schematics, diagrams, graphs, and photographs (7 in colour) enhance the text. …The authors have succeeded in putting this fine work together. It is filled with a wealth of interesting, relevant and practical information and I would consider it mandatory reading for anyone already within or about to enter the field of xenobiochemistry.”

—Steve Mitchell, Imperial College London, South Kensington, UK, the ISSX (International Society for the Study of Xenobiotics) Newsletter, Winter 2006 / Spring 2007 edition

Table of Contents

Radiotracers and Drug Registration, Graham Lappin

The Drug Registration Process

Drug Metabolism

Origins of Radiotracer Studies

New Chemical Entities and Biopharmaceuticals

What Are Radiotracers Used for in Drug Registration?

Detection of Radioactivity

The Regulatory Position of Metabolism Studies



Radioactivity and Radiotracers, Graham Lappin

Atoms and Isotopes

Isotope Stability

Types of Radioactive Decay


Units of Radioactivity

Units of Dose


Specific Activity

Maximum Theoretical Specific Activity

Universal Quantification

Calculation of Limits of Detection (LOD)

Synthesis of Radiolabeled Compounds

Radiopurity and Autoradiolysis

Kinetic Isotope Effects

Further Reading



The Study of Drug Metabolism Using Radiotracers, Graham Lappin


Choice of Radiolabel

Test Systems

In Vitro Studies

In Vivo Studies: Experimental Aspects

In Vivo Studies:Data Interpretation

Structural Alerts

Appendix 1: An Overview of Xenobiotic Biotransformations

Appendix 2:Examples of Xenobiotic Metabolism Studies from the Literature

Appendix 3:Pharmacokinetics



DNA Binding, Isotope Dilution, and Other Uses of Radiotracers, Graham Lappin


DNA Binding


Gel Blotting

Isotope Dilution

Miscellaneous Uses


Quantitative Whole-Body Autoradiography (QWBA), Brian Whitby


Principles and History of QWBA

The Modern Technique of Whole-Body Autoradiography

Some Specific Uses of the QWBA Technique

Microautoradiography5.6 Summary

Appendix 1: Dosimetry Calculations for the Administration of Radioisotopes to Humans



Scintillation Counting, Simon Temple


How Does Scintillation Counting Work?

Photomultipliers and Accompanying Circuitry

Spectrum Analysis and the Introduction of the Multichannel Analyzer



Interferences in Scintillation Counting


Wall Effect

Cherenkov Counting

Dual-Label Counting

Gamma Counting

ß–-Counting with Solid Scintillators

Multiwell Plate Scintillation Counting

Flow Scintillation Counting


Statistics in Liquid Scintillation Counting, Simon Temple


Standard Deviation

Use of %2ó in Scintillation Counting

Low Activity Counting

Limits of Detection


Instrumentation for Detection of Radioactivity, Simon Temple



Background Reduction

Quench Correction: General Considerations

Quench Correction without an External Standard

Methods of Quench Correction Using External Standards

Solid vs. Liquid Scintillation Counting

Microplate Scintillation Counters

Flow Scintillation Counting

Stationary Eluate Analysis

Multicell Eluate Analysis

Wire Scanners


Appendix 1: List of Instrument Manufacturers and Suppliers


Sample Preparation for Liquid Scintillation Counting, Simon Temple


Solubilization vs. Oxidation

General Considerations


Whole Blood and Bile

Plasma and Serum

Biological Tissues


Noncommercial Solubilizers


Biomedical Accelerator Mass Spectrometry, Graham Lappin

The Beginnings of Accelerator Mass Spectrometry

AMS Instrumentation


Sample Preparation

Data Handling

Sensitivity and Precision of AMS

The First Biomedical AMS Studies

AMS and Drug Development



Positron Emission Tomography, Barbara S. Koetz and Patricia M. Price


General Principles of PET

Spatial Resolution and Detectors

Data Gathering and Interpretation

Isotope Generation Using a Cyclotron

Choice of Radioisotopes

Labeled Ligand and Drug Synthesis

PET Application: Pharmacokinetic Studies

Pharmacodynamic Studies


Gamma Scintigraphy and SPECT, Stephen P. Newman and Gary R. Pitcairn

The Development of Scintigraphic Imaging

Data Gathering and Interpretation

Applications to Formulation Design


About the Authors/Editors

Lappin\, Graham; Temple\, Simon

Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Pharmacology
MEDICAL / Radiology & Nuclear Medicine
SCIENCE / Chemistry / General