Quality control of PET radiopharmaceuticals, with reference to its specifics vs quality control of conventional pharmaceuticals

Abstract

Radiopharmaceutical preparations or radiopharmaceuticals are medicinal products which, when ready for use, contain one or more radionuclides (radioactive isotopes) included for a medicinal purpose. As well as pharmaceuticals, they undergo strict quality control (QC) tests and procedures before release for use in patients. PET radiopharmaceuticals are usually formulated as sterile, apyrogenic injections, so they have to fulfill requirements for quality, efficacy and safety of conventional parenteral preparations.

The specifics of QC of the radiopharmaceuticals arise from the very nature and the short half-life of the radioisotopes. The presence of radioisotope require introducing tests for radionuclidic and radiochemical identity and purity which are unique for radiopharmaceuticals. The presence of undesirable, extraneous radionuclides increases the undue radiation dose to the patient and may also degrade the scintigraphic images.

Radionuclidic purity (RNP) is defined as the fraction of the total radioactivity in the form of the desired radionuclide present in a radiopharmaceutical, usually expressed as a percentage. RNP is determined by measuring the half-lives and emitted gamma radiation (gamma spectroscopy method).

Radiochemical purity (RCP) is the fraction of the total radioactivity in the desired chemical form in the radiopharmaceutical. For most radiopharmaceuticals, radiochemical purity above 95 % is desirable, since the impurities will almost certainly have a different biodistribution which can distort the image and interfere with the interpretation of the scan. Determination of the radiochemical purity can be carried out by a variety of chromatographic methods like TLC, HPLC.

Unlike conventional pharmaceuticals, radiopharmaceuticals cannot be manufactured, then tested and left in quarantine until the results of all tests are available, as most (if not all) of the radioactivity will decay to a level when this radiopharmaceutical will become useless. The radiopharmaceuticals have to be manufactured, tested for quality and then administered to the patient within a short period of time. Since the execution of some of the tests takes more time, it is not mandatory these tests to be completed before release for use. These tests are strictly defined in the individual pharmacopeia monographs.

In addition, due to the presence of source of radiation, all aspects of radiation protection should be retained while doing the tests for quality control of radiopharmaceuticals.

Key words: radiopharmaceuticals, QC control, radioisotope, radionuclide impurity, radiochemical impurity, radiation protection,