3D ultrasonic molecular imaging to assess the efficacy of an aurora kinase inhibitor in pancreatic adenocarcinoma

摘要

Most early phase trials use the change in tumor volume as a measure for disease response. However, it is difficult to evaluate the true efficacy of drug therapies with tumor size measurements alone. Since ultrasonic molecular imaging (MI) can provide information prior to the appearance of gross phenotypic changes, it is proposed that MI can be used to noninvasively assess early response to treatment. 10 nude mice with patient-derived tumorgrafts were used for MI experiments. 5 animals received a dose of 30 mg/kg of MLN8237 each day over a 48 hour period while the remaining animals were treated with a control vehicle. 3D MI was performed on day 0 and 48 hours after treatment using size-selected microbubble contrast agents (MCAs) fitted with a cyclic RGD peptide targeted to αvγ3, an angiogenic biomarker. At 48 hours, mean volumetric targeting decreased by 62% from baseline in treated animals compared to an 8% decrease in targeting for untreated animals (Untreated: 0.92±0.22 vs Treated: 0.38±0.23; p < 0.05). Measured volume increased by 3% in treated animals as compared to a 9% increase from baseline in untreated animals (Untreated: 1.09±0.13 vs Treated: 1.03±0.03; p > 0.05). Monitoring volumetric changes is the “gold standard” for evaluating treatment, however, our data suggests that MI may provide information about tumor response at earlier timepoints.