Microfluidic systems for high efficiency radiolabeling and purification of nanomedicines

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One method of investigating disease pathways or diagnosing diseases is imaging using single photon emission computed tomography (SPECT). With SPECT, a gamma-emitting radioisotope is connected to or incorporated into a molecule, a macromolecular compound, or a compound in the nano- to micro-meter range. Most often, this radiolabeling step is accomplished using a kit format, where the radioactivity is added to a vial of all the other ingredients to quickly obtain the radiolabeled compound and this compound is then injected into an animal or patient. The kit format, however, cannot always be used, as the introduction of the radioisotope might change the properties of the final radiolabeled compound, or the chemistry of the system might not allow for an efficient radiolabeling procedure (multiple steps required, radiation hazard, air sensitive, separation steps needed). This project aims to build a microfluidics micro-/nanodevice to overcome difficulties of radiolabeling and purifying radiopharmaceuticals that include nanoparticles, microspheres, and macromolecular compounds. We will carefully integrate the radiolabeling step inside microfluidic channels, which will be optimized for diffusion and reaction kinetics. We will also, if necessary, apply forced mixing on built-in mixing structures, use a built-in heatable reactor feature, and concentrate and separate the resulting compounds and nanomedicines with microfluidic Dean forces, based on our recent research in this field. An additional separation feature might be the use of local magnetic forces. The aim is to improve on the ease of procedure and the radiolabeling efficiency, while at the same time allowing for ideally aseptic conditions and ease of quality control. The resulting radiopharmaceuticals will be compared to the conventional techniques in terms of material use (which is hypothesized to be much less), reaction time (likely shorter), and radiolabeling efficiency (likely higher). Different radioisotope systems will be investigated, with rhenium-based ones (for example Re-188) being at the forefront. Currently, their oxidation sensitivity (back to water soluble perrhenate) is a problem, and will be optimized for future therapeutic applications. Microfluidic based methods for the preparation of diagnostic and therapeutic radiopharmaceuticals might thus be crucial to allow for high enough radiation concentrations, and provide truly theranostic agents for future detection and treatment of cancer.