@article{Oronsky2026, 
author = {Bryan Oronsky and Dandan Li and Morgan Wang and Jenny M. Vo-Phamhi and Scott Caroen and Nacer Abrouk and Tony Reid and Babak Alizadeh and Dimitre Hristov and George Fisher and Ahmed El Kaffas},
title = {3D Dynamic Contrast-Enhanced Ultrasound for Personalized RRx-001 Dosing: A Preclinical and Clinical Pilot Study},
year = {2026},
journal = {Advanced Ultrasound in Diagnosis and Therapy},
volume = {10},
number = {3},
pages = {169-177},
keywords = {Ultrasound, Vascular normalization, Contrast-enhanced ultrasound, Oncology, Tumor vasculature},
url = {https://www.sciopen.com/article/10.26599/AUDT.2026.250086},
doi = {10.26599/AUDT.2026.250086},
abstract = {Background and Purpose Tumor blood vessels are abnormal and contribute to therapy resistance. RRx-001, an NLRP3 inhibitor, has been shown to remodel tumor vascular properties, enhancing the effects of cytotoxic or immune-promoting agents. However, optimizing timing and dosing of combined treatment regimens is challenging on a patient-by-patient basis; tools for longitudinal imaging to guide such treatment strategy are necessary. Our aim was to evaluate the feasibility of 3D dynamic contrast-enhanced ultrasound (3D DCE-US) to detect acute and subtle tumor perfusion changes following RRx-001 therapy in both mice and humans.Methods RRx-001 was administered intraperitoneally at varying doses to determine its effect on perfusion in a mouse model of colon cancer. Blood flow and volume were assessed semi-quantitatively using 3D DCE-US within hours and at subsequent time-points. Additionally, we assessed 3D DCE-US in three patients enrolled in a Phase 2 RRx-001 clinical trial (NCT02096354) by imaging them longitudinally.Results In mice (n = 38), 6 mg/kg RRx-001 led to a 1.5% increase in AUC (P = 0.02) and MTT at 24 hours; 12 mg/kg showed no acute effect. In patients (n = 3), 66 mg weekly dosing produced variable perfusion changes within hours to days. Two patients with stable disease showed transient perfusion increases (survival 9-15 months); one with progressive disease showed early perfusion loss (survival 4 months). No grade 3/4 toxicities occurred.Conclusion These findings highlight the potential of 3D DCE-US as a noninvasive, bedside tool for real-time monitoring of RRx-001-induced perfusion changes, supporting the feasibility of personalized dosing strategies in both preclinical and clinical settings.}
}