Development and validation of radiochemical methods for the preparation and use of pet radiopharmaceuticals

The availability of short-lived radioisotopes for positron emission tomography from a parent/daughter radionuclide generator system offers a convenient alternative for obtaining clinically relevant PET tracers for imaging centers that lack an costly local cyclotron. A clinical useful and reliable radioisotope generator should be cost-effective, transportable, easy to handle, and provide tracers on-demand. In the first part of the study, the performance of both a commercially produced 62Zn/62Cu microgenerator system, and a kit-based synthesis method, in clinical site production of 62Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational new radiopharmaceutical for PET perfusion imaging, were thoroughly examined. The development of two alternative quality control methods (C18 SepPak and Thin Layer Chromatography) for a 62Cu-ETS radiochemical purity assay are also reported. The data gathered from this work demonstrates the 62Zn/ 62Cu microgenerator to be a reliable source of positron-emitting 62Cu under the conditions of clinical use. Additionally, the rapid kit-based 62Cu-radiopharmaceutical synthesis has been a convenient, and highly reliable, \u27on-demand\u27 source of 62Cu-ETS for PET perfusion imaging. Copper-62 is attractive in PET imaging because its 10 minutes of half-life is compatible with longer image acquisition period, and short enough to also allow repeat studies at brief time intervals. The parent nuclide, Zinc-62 has a half-live of 9.2 hours, allowing it to be manufactured in a centralized production site under good manufacturing practices guidelines, and to be transported over fairly long distance. The second part of the study focused on the development and validation of analytical methods for determination of the 11CO2-metabolites generated in blood following intravenous administration of cyclotron-produced [11C]acetate and [11C]palmitate PET radiopharmaceuticals. Carbon-11 carbon dioxide can a major radioactive metabolite generated following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate PET radiotracers. The fraction of 11C-activity present as [11C]CO2 in arterial blood needs to be measured in order to obtain a correct radiotracer arterial input function for quantitative analysis of the rate of tissue metabolism. However, arterial puncture for blood sampling is often undesirable. The first goal of this study was to test the reliability of a reported 10-min gas-purge method used to assay [11C]CO2-radioactivity in blood. To do this, fresh collected porcine blood samples were spiked with pure [ 11C]CO2, [11C]acetate, or [11C]-palmitate. The total 11C-radioactivity was counted in samples treated with sodium hydroxide solution, while the fraction of [11C]CO 2 was measured after the blood was treated with hydrochloric acid, followed by 10-minute of gas purge for [11C]CO2 removal. As predicted, more than 99% of [11C]CO2 was removed from the acid-treated blood samples, while all of the [11C]acetate and [11C]palmitate radioactivity was retained in the acid treated samples. Our second goal was to establish whether venous blood could substitute for arterial blood in sampling to estimate the levels of arterial [ 11C]CO2 after the i.v administration of [11C]acetate and [11C]palmitate. We compared the results of [11C]CO 2-metabolite analyses performed on simultaneously collected arterial and venous blood samples. Using a pig model, paired arterial and venous blood samples were drawn at 1, 3, 6, 8, 10, 15, 20, 25 and 30 minutes post i.v administration of [11C]acetate or [11C]palmitate, and the fraction of [11C]CO2 was measured according to the validated gas-purge method. (Abstract shortened by UMI.