Table 1

Patient Characteristics: stable disease (SD) and progressive disease (PD)"

Table 2

Mean 3D-DCE-US patient measurements of regional blood volume (RBV) and regional blood flow (RBF)"

Figure 1

(A) 3D DCE-US detects dose-dependent changes in tumor perfusion parameters following RRx-001 treatment in mice. All animals available for control (n = 16) vs. 6 mg/kg (n = 13) vs. 12 mg/kg (n = 9) for each of 4 bolus-perfusion parameters shown as percent difference relative to baseline at 4 hrs and 24 hrs. Trend is noted in overall increases in perfusion parameters in mice receiving RRx-001. Peak enhancement (PE) reflects a measure of blood volume at the highest peak while area under the curve (AUC) represents total blood volume flowing in tumor from wash in to wash out. While a trend is noted for PE and AUC within 4 hours after treatment, AUC at 24 hours after treatment was the only one significant parameter (P = 0.02; compared to control at 24 hours after baseline). Time-to-peak (TP) is proportional to blood flow at wash-in and mean transit time (MTT) represents the total time it takes contrast to wash in and wash out (also a measure of blood flow). While increases in blood flow (i.e., faster wash-in and longer wash-out) are noted after RRx-001, these were not significant. Error bars are standard errors of the mean (SEM). Significance is represented as *P = 0.02 (Mann-Whitney test); (B) Contrast ultrasound image at peak enhancement of ~25 mm lesion on hind leg of animal viewed in sagittal, coronal, and axial planes. The yellow volume of interest designates the lesion in 3D."

Figure 2

Longitudinal 3D DCE-US reveals heterogeneous patient-specific perfusion responses to RRx-001 over two weeks. Panel A shows representative snapshot images from scan 00 (baseline), scan 01 (2-4 hours), scan 02 (7 days) and scan 03 (2 weeks) from the 3D-DCEUS of patient 2, and Panel B shows the same of patient 3, and Panel C is the perfusion TIC for patients 1, 2 and 3. The blue curve represents baseline scans before any RRx-001 treatment administration, the red curve represents 2-4 hours post first treatment, the green curve is 7 days post treatment and the purple curve 2 weeks after initial treatment. Note from C the drastic differences in baseline perfusion, and the change in perfusion for each patient. The same Philips EPIQ7 system and X6-1 transducer were used with the same imaging parameters as in mice, with the exception of custom adjustments to the focus and depth of imaging."