(350f) Radiolabeling of Biomolecules with Cu-64 in Microfluidic Reactors
AIChE Annual Meeting
2009
2009 Annual Meeting
Nuclear Engineering Division
Chemical Engineering Advances in the Nuclear Fuel Cycle (including NED student competition)
Wednesday, November 11, 2009 - 10:10am to 10:30am
Radiolabeled biomolecules are used for Positron Emission Tomography (PET), a medical diagnostic technique used to image tumors in the body, and as radiotherapeutic agents. The radiolabeled biomolecules used in these applications consist of a peptide or antibody coupled to a bi-functional chelator (BFC) that chelates a radioactive metal ion. Once introduced into the body, the biomolecule binds to receptors that are expressed on the surface of cancerous cells, thereby targeting the delivery of the radiometal. Among radiometals, copper-64 (Cu-64) is one of the most widely used isotopes for PET imaging, due to its simple and well-understood coordination and redox chemistry, and ability to form kinetically inert copper complexes for long term targeting and trapping (e.g. radiolabeled antibodies).
In conventional radiolabeling procedures, a large excess of the BFC (approximately 100 fold) is typically used for convenient handling of the chemicals and efficient radiolabeling. However, this excess results in lower specific activity of the radiolabeled probe, slower reaction times, and high consumption of expensive precursors. In order to improve the specific activity and image low abundance targets in vivo, extensive and time consuming separation procedures are required.
In this presentation, we will discuss the development of microfluidic reactors for efficient radiolabeling of biomolecules with Cu-64, and demonstrate higher specific activities than obtained in conventional, macro-scale processes. We will also demonstrate that the microfluidic approach allows for reduced consumption of expensive precursors, and synthesis of clinically relevant volumes (~50 ìL) and concentrations of solutions of radiolabeled biomolecules. The integration of various radiolabeling steps on a single system leads to improved automation of the radiolabeling process. We will conclude with a discussion on further potential improvements to the production of radiolabeled biomolecules through the application of microfluidic technologies.