Monitoring tumor response to the vascular disrupting agent CKD-516 in a rabbit VX2 intramuscular tumor model using PET/MRI: Simultaneous evaluation of vascular and metabolic parameters

OBJECTIVES: To determine whether the CKD-516 produces a significant change in vascular and metabolic parameters in PET/MRI MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 18 VX2 carcinoma tumors implanted in bilateral back muscles of 9 rabbits were evaluated. Serial PET/MRI were performed before, 4 hours after and 1-week after vascular disrupting agent, CKD-516 at a dose of 0.7 mg/kg (treated group, n = 10) or saline (control group, n = 8) administration. PET/MRI-derived parameters and their interval changes were compared between the treated and control group by using the linear mixed model. Each parameter within each group was also compared by using the linear mixed model. RESULTS: Changes of the volume transfer coefficient (K(trans)) and the initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) in the treated group were significantly larger compared with those in the control group at 4-hour follow-up (mean, -39.91% vs. -6.04%, P = 0.018; and -49.71% vs. +6.23%, P = 0.013). Change of metabolic tumor volume (MTV) in the treated group was significantly smaller compared with that in the control group at 1-week follow-up (mean, +118.34% vs. +208.87%, P = 0.044). Serial measurements in the treated group revealed that K(trans) and iAUC decreased at 4-hour follow-up (P < 0.001) and partially recovered at 1-week follow-up (P = 0.001 and 0.024, respectively). MTV increased at a 4-hour follow-up (P = 0.038) and further increased at a 1-week follow-up (P < 0.001), while total lesion glycolysis (TLG) did not show a significant difference between the time points. SUVmax and SUVmean did not show significant interval changes between time points (P > 0.05). CONCLUSIONS: PET/MRI is able to monitor the changes of vascular and metabolic parameters at different time points simultaneously, and confirmed that vascular changes precede the metabolic changes by VDA, CKD-516.