Multiparametric MRI biomarkers for measuring vascular disrupting effect on cancer

Figure 1 Schematic mechanisms of action with tubulin-binding vascular disrupting agents. VE: Vascular endothelial; VDAs: Vascular disrupting agents; EC: Endothelial cell.

Figure 2 In vivo magnetic resonance imaging findings of an implanted tumor in rat liver. Before treatment, the tumor (arrows) appeared hyperintense on T2WI (A1); hypointense on T1WI (A2); strongly enhanced on CE-T1WI (A3); and slightly hypointense on ADC_high (b = 500, 750, 1000 s/mm²) (A4). At 24 h after the intravenous treatment with CA4P at 10 mg/kg, obvious vascular shutdown was observed. The tumor (arrows) was still hyperintense on T2WI (B1) and hypointense on T1WI (B2). On CE-T1WI, the tumor (arrow) appeared hypointense in the center with an enhanced rim of viable neoplastic cells (B3). On ADC_high map (B4), the hyperintensity in the center corresponded to necrosis, and the isointense ring was concordant with the viable tumor rim (arrow) on CE-T1WI. Note the viable tumor nodule at the periphery, shown as hyperintensity (arrowhead) on CE-T1WI (B3), and hypointensity (arrowhead) on ADC_high (B4).

Figure 3 ADC_perfusion and initial area under the gadolinium curve in an implanted tumor in rat liver. At 48 h after iv treatment with CA4P at 10 mg/kg, obvious tumor recurrence with partial recovery of blood supply was demonstrated. The tumor (arrows) appeared hyperintense on T2WI (A) and hypointense on T1WI (B); On CE-T1WI, the tumor relapsed at the periphery, shown as ring enhancement of viable tumor cells (C); ADC_10b (derived from 10 b values from 0 to 1000 s/mm²) revealed the hyperintense necrotic center and isointense viable tumor rim (D); On ADC_perfusion (ADC_low-ADC_high) maps, the relative hyperintensity at the periphery suggested the partial recovery of perfusion, compared to the hypointensity in the necrotic center with perfusion deficit (E); ADC_perfusion matched well with CE-T1WI-overlyaed initial area under the gadolinium curve (IAUGC) map (F).

Figure 4 Dynamic changes in K^trans. The tumor (arrows) in rat liver showed an abundant blood supply with high K^trans before treatment (A); At 6 h after CA4P treatment, vascular shutdown was indicated with low K^trans in the center, surrounded by tumor residue at the periphery, with moderate K^trans (B); At 48 h after treatment, the tumor relapsed upon the residue at the periphery with rebounding K^trans (C).