A multi-organ microphysiological system for radiopharmaceutical biodistribution studies

Abstract

Radiopharmaceuticals play a crucial role in positron emission tomography for diagnostic imaging and targeted cancer therapy. Their biodistribution and metabolism must be thoroughly characterized during preclinical development. While conventional studies rely on animal experiments, microphysiological systems offer a humanrelevant in vitro alternative. This study presents a multi-organ MPS comprising tumor, liver, and kidney equivalents for radiopharmaceutical testing. Micro-particle image velocimetry confirmed that the microfluidic design achieves the intended volume flow distribution with deviations below 1 percentage point across all compartments. Static monolayer experiments demonstrated specific, GLUT-mediated [ ¹⁸ F]FDG uptake in all three organ equivalents, validated by competitive glucose blocking. Under dynamic flow conditions, phosphor imaging revealed homogeneous tracer distribution during circulation and compartment-specific [ ¹⁸ F]FDG retention exclusively at the organ equivalent positions. These results provide a biological proof-of-concept for the use of multi-organ-microphysiological systems as a physiologically relevant, animal-free platform for preclinical radiopharmaceutical biodistribution studies.