Quantitative computed tomography analysis of local chemotherapy in liver tissue after radiofrequency ablation

Computed tomography (CT) was used to noninvasively monitor local drug pharmacokinetics from polymer implants in rat livers before and following radiofrequency ablation. Polymer matrixes containing carboplatin (a platinum-containing chemotherapeutic agent) were implanted into rat livers either immediately after radiofrequency ablation (n = 15) or without prior treatment (n = 15). The animals were divided into five subgroups (n = 3 per group) and subjected to a terminal CT scan at 6, 24, 48, 96, or 144 hours. Carboplatin concentration in tissue and within the implant matrix was correlated with CT intensity, and standard curves were produced for each environment. This correlation was used to evaluate the differences in drug transport properties between normal and ablated rat livers. A quantitative image analysis method was developed and used to evaluate the release rate and tissue distribution of carboplatin in normal and ablated liver tissue. The CT data were validated by previously reported atomic absorption spectroscopy measurement of implant and tissue drug levels. Correlation of carboplatin concentration and Hounsfield units results in a linear relationship with correlation coefficients (slopes) of 15 and 4 Hounsfield units/(mg/mL), for carboplatin in tissue and polymer, respectively. Noninvasive monitoring of local pharmacokinetics in normal and ablated tissues indicates that ablation before local carboplatin delivery increases the retention of carboplatin within the polymer matrix and drastically increases the drug retention in the ablated tissue volume (over 3-fold difference) resulting in a higher average dose to the surrounding tissue. At 1.6 mm from the implant boundary, carboplatin concentration is significantly higher in ablated tissue at 48, 96, and 144 hours (P <.05), and reaches 4.7 mg/mL in ablated tissue at 48 hours. In comparison, the concentration in normal liver at 1.6 mm reaches only 0.7 mg/mL at the same time point. The drug penetrates 3.1 mm in ablated liver compared with 2.3 mm in normal liver also at 48 hours. After 144 hours, the drug is still detected at 3.1 mm in ablated liver but not in normal liver. The differences are significant (P <.05) at both 48 and 144 hours. Correlation with chemical analysis suggests that CT data accurately predicts the drug pharmacokinetics in both ablated and normal livers. This work shows that X-ray CT imaging is a useful and promising technique for in vivo monitoring of the release kinetics of locally delivered radiopaque agents.