Single-use Microfluidic Device for Radiopharmaceutical Production

ABSTRACT Radiopharmaceuticals (RPs) are essential linchpins of cancer diagnosis, staging, and therapy. For diagnosis, the sensitivity and quantitative nature of positron emission tomography (PET) imaging, coupled with the ability to produce biologically active RPs bearing positron-emitting isotopes, renders PET uniquely capable of detecting tumors and quantifying their actionable molecular features. Moreover, recent successes in theranostics(1), which utilize targeted RP pairs for diagnosis and therapy, have led to improved outcomes in challenging clinical settings, such as neuroendocrine and prostate cancers(2, 3). Encouraged by these results and recent clinical approvals, pharma and academia alike are investing heavily in RP Research and Development (R&D) in pursuit of theranostics targeting other solid tumors, such as pancreatic(4, 5), breast(6), and lung cancer(7). Due to the immense infrastructure, resource, and logistical burdens associated with current strategies for radiopharmaceutical production (including PET imaging diagnostics and radionuclide therapeutics), the development and proliferation of radiopharmaceuticals beyond routine diagnostics such as [18F]FDG is challenging and expensive. The vast infrastructure required to develop, evaluate, and deliver radiopharmaceuticals, and even radioisotopes themselves, severely limits their deployment to the patients that need them(8). To address this critical hurdle, we will develop a rapid, inexpensive microfluidics-based approach for dose-on-demand production of human dosage quantities of ready-to-inject radiopharmaceuticals that can be adapted to a variety of radiopharmaceutical-related chemistries. In addition to facilitating end-user manufacturing and purification with a minimum of resources, the proposed platform will simplify raw isotope distribution logistics by using the chip itself as the shipping container and as the module for purifying (and eventually reacting) the desired radiometal. The objective of this proposal is to dramatically reduce barriers associated with RP production, rendering RP discovery and dissemination dramatically more accessible. To achieve these goals, we will build upon our prior development of the radiometal sub-family of simple, inexpensive, microfluidic ‘single dose-single device’ radiosynthesis platform RAPID-M (Radiopharmaceuticals As Precision Imaging Diagnostics-Metals). Based upon our published and preliminary studies, our Specific Aims are: To employ RAPID-M as a “ship-on-chip” device for simple isotope purification, transport and downstream, end-user application (Aim 1); to demonstrate RAPID-based synthesis of a theranostic pair for imaging and therapy (Aim 2); and to automate the RAPID concept to allow for production of RPs with minimal operator intervention (Aim 3).