Journal of Labelled Compounds and Radiopharmaceuticals J Label Compd Radiopharm 2007; 50: 679–682. Published online 4 June 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.1309 JLCR Note A SepPak unit for batch processing serial blood plasma samples for PET JOHN R. GRIERSON*, LINDA WIENS, LANELL PETERSON and HUBERT VESSELLE Department of Radiology, University of Washington, Seattle, WA 98195, USA Received 24 January 2007; Revised 20 February 2007; Accepted 26 February 2007 Abstract: A prototype blood plasma processor unit was designed and tested for generic PET-tracer metabolite analyses, using solid-phase-extraction cartridges (SepPaks). An assay method for FLT (3 0 -deoxy-3 0 -[F-18]fluor- othymidine) and its blood metabolite: FLT-glucuronide, in serial, patient-derived samples was developed to evaluate the device. The unit is simple to construct from readily available components and can process up to six samples in parallel for high throughput. The precision of sample results was evaluated in a test–retest trial and was 98%. A syringe pump method for sample application and SepPak elution proved to be a reliable technique. Copyright # 2007 John Wiley & Sons, Ltd. Keywords: PET; plasma metabolite; SepPak; FLT; sample processor Introduction To perform a kinetic analysis of dynamic PET imaging data it is essential to follow the declining fraction of blood plasma activity that is specific to the parent radiopharmaceutical, and sometimes a specific meta- bolite. 1 Typically, eight to 12 serial blood plasma samples need to be analyzed to construct the appro- priate plasma input function(s). The number of sam- ples required is dictated by the curvature of the blood time–activity curve, the rapidity of drug metabolite production, the time required for sample processing and the half-life of the radionuclide. In the setting of a busy PET imaging suite, limited access to a shared counting instrument may also be a factor. Rapid solid-phase-extraction (SPE) methods for drug metabolite analysis 2 offer a practical, cost-effective alternative to time-consuming HPLC methods. How- ever, processing of multiple samples can also be challenging and requires considerable focus to avoid handling errors. Herein, we report on the design and testing of a versatile multi-sample SPE processor unit. This portable unit was easily assembled from standard parts. It has been used for routine metabolite analysis of [F-18]FLT (3 0 -deoxy-3 0 -[F-18]fluorothymidine) in PET studies. The unit separates FLT from its glucuronide conjugate in diluted plasma samples. Results and discussion SPE methods are used to process samples, such as blood plasma, by extracting or voiding a desired analyte. A variety of SPE stationary phases are avail- able for extracting ionic or lipophilic species. For convenience, multiple samples are typically processed in parallel using a panel of SPE cartridges connected to a vacuum manifold. However, flow control through these cartridges poses problems. For example, sample breakthrough is an issue when flow is too fast or crudely controlled. Cartridge packing densities may also differ, which leads to a range of flow and performance. This can cause incomplete sample ex- traction and result in poor quantitation. To standardize our use of SepPak cartridges for SPE, we designed a unit that relies on syringe pumps to better control fluid flow through the SepPaks. The device schematic and the physical layout are shown in Figures 1–3. Up to six samples can be processed at once. The specific configuration uses a tandem pair of SepPaks (anion exchange-QMA and C18) to separate FLT–glucuronide (FLT-G, a blood metabolite) from FLT, respectively. In our experience, the syringe pump *Correspondence to: John R. Grierson, Department of Radiology, University of Washington, UW Medical Center Room RR215, 1959 NE Pacific Street, Seattle, WA 98195, USA. E-mail: grierson@u.washington.edu Contract/grant sponsor: NIH; contract/grant numbers: CA107264 and CA115559 Copyright # 2007 John Wiley & Sons, Ltd.