Positron Emission Tomography (PET) is a medical imaging modality widely used in cancer diagnostics. Oncological applications of PET include treatment planning, tumor staging and treatment efficacy evaluation. Availability of the procedure is limited by the supply of a short-lived radioactive contrast agent (18F-FDG). Trace-Ability is developing a solution that eliminates limitations in the supply of 18F-FDG and thus makes personalized medicine accessible for more cancer patients. The main focus of the proposed project is an automated platform for quality control of 18F-FDG. 18F-FDG production has to be performed daily due to the 2-hour half-life of 18F. Fourteen quality control tests are often the bottleneck of the production. Correct execution of this diverse set of procedures requires highly qualified and experienced facility personnel. Our approach is to develop a set of tests amenable for automation on commercially available hardware. This development concept is drastically different from the methods of our competitors, who rely on automation of existing tests and have to face the difficulties of the ground-up engineering, software development and hardware validation. Hardware platform chosen for this project include two analytical instruments: liquid chromatograph and plate reader. Combined with a liquid handling robot, this platform will be able to perform full QC testing if 18F- FDG. A single-use kit of reagents will enable GMP compliant operation of the platform. In this proposal we focus on proving feasibility of the last three tests never performed on a plate reader: radionuclide identity (half-life), radioactivity concentration and kryptofix concentration.
Specific Aim 1 : Establish feasibility of the radiation intensity measurement using the luminescence reading mode of a plate reader. We propose to use Liquid Scintillation Counting to measure 18F concentration and half-life. We hypothesize that due to the high energy of positrons emitted from 18F, a dedicated Liquid Scintillation Analyzer is not needed and that a plate reader in luminescence mode will be sensitive enough to accurately quantify 18F concentration. Therefore, the same plate reader used to quantify other QC parameters could be used to determine radionuclide identity and radioactivity concentration.
Specific Aim 2 : Establish feasibility of the kryptofix quantification using the absorbance reading mode of a plate reader. The current kryptofix test can hardly be automated: this is a multistep process and it relies on formation of a colored solid. We propose to develop a solution indicator that changes its color according to kryptofix concentration. We hypothesize that a metal - metal ion indicator complex can be used for this purpose. Formation of a metal+indicator complex will determine the absorption spectrum. Kryptofix can scavenge metal ions, increasing relative concentration of the free indicator. The resulting spectral shift wll be detected by the plate reader in the absorbance mode.
Positron Emission Tomography (PET) is a unique diagnostic procedure critically important for accurate cancer diagnostics and treatment planning. Availability of PET is limited by labor intensive production of the radioactive contrast agent used in this procedure. Proposed project aims to alleviate this shortcoming by introducing an automated system for quality control of the contrast agent, resulting in expanded availability of PET to more cancer patients.
