Radioisotope labeled drugs

Preparation of Radioisotope Labeled Drugs Richard C. Thomas I, 296 ... 

The ultrahigh sensitivity of AMS enables it to follow trace amounts of radioisotope-labeled drugs in animals and humans postadministration. In addition to microdose PK studies, AMS has been utilized in many aspects of pharmaceutical research, such as absolute bioavailability determination, mass balance and metabolite profiling, and identifications of DNA and protein adducts. 

This report Is concerned with the preparation of radioisotope-labeled drugs for use as drug tracers, not of radiopharmaceutical agents for use in diagnosis and therapy. Since this has not been the subject of previous reports in this series, particular attention will be given to general principles. 

Design of Synthesis - In using a radioisotope-labeled drug as a tracer one ordinarily is concerned with following the carbon skeleton of the drug molecule. To accomplish this, usually only one of the atoms in the molecule is labeled to serve as the tracer for the entire molecule. 

In the enzyme-multiplied immunoassay techniques (EMIT), the antigen or antibody is labeled with an enzyme (e.g., iysozyme, alkaline phosphatase, horseradish peroxidase, or glucose-6-phosphate dehydrogenase) instead of a radioisotope. For example, an alkaline phosphatase-labeled drug can be made to compete with an unlabeled drug for binding sites on... 

Besides commercial kits, many immunochemical reagents are available (191,192) anti-drug antibodies, anti-enzyme antibodies, radioisotopic labels, nonisotopic labels, secondary antibodies, and biotinylated conjugates. Because of the flexibility in IA designs, investigators can consider several options from the availability of the commercial materials in addition to in-house resources in preparing the IA reagent components. 

Table 4.1 characteristics of radioisotopes commonly used for labelling drugs... 

The total amount of labeled drug to prepare, in terms of radioactivity, depends on the anticipated studies, the radioisotope, and methods for detecting the radioactivity. In a typical drug-metabolism study Involving 3 animal species and man, using liquid scintillation counting techniques, approximately one mCi of a carbon-14 or sulfur-35 labeled drug will suffice. Similar studies with tritium would require 2 to 4 mCl since the detection efficiency for tritium by the same techniques is only one-half to one-fourth that for carbon-14 and sulfur-35. 

For this method, the drug candidate is labeled with a radioisotope, such as carbon-14. The AD ME of the compound within the body can be monitored by analyzing samples using high sensitivity instrumentation, for example, accelerator mass spectroscopy. 

---