Quantification of PSMA expression in prostate cancer by pharmacokinetic modeling of targeted ultrasound nanobubbles

The value of contrast-enhanced ultrasound (CEUS) for prostate cancer diagnostics is still debated. Novel targeted ultrasound contrast agents enable visualization of molecular and cellular processes in vivo and non-invasively. Microbubbles targeted to the vascular endothelial growth factor receptor 2 have been successfully tested in humans, but detection rate for prostate cancer was limited to 65%. While microbubbles can only target molecules in the blood vessels, novel nanobubbles (NBs) can extravasate, thus enabling reaching targets beyond the vessel wall. Recently, NBs targeted to the prostate specific membrane antigen (PSMA), which is overexpressed by prostate cancer cells, have shown selective accumulation in prostate-tumor mouse models. However, methods for quantification of NB binding are still lacking. In this work, we propose a pharmacokinetic modeling approach to estimate the binding potential of PSMA-targeted NBs, and we test the proposed method in 7 dual-tumor mouse models of prostate cancer.