Variability of apoptosis and response in N1-S1 rodent hepatomas to benzamide riboside and correlation to early changes in water apparent diffusion coefficient and sodium MR imaging

Purpose: This pilot trial assesses variability of apoptosis and response 1 day after hepatic intraarterial (IA) benzamide riboside (BR) in rodent hepatomas and its correlation to water apparent diffusion coefficient (ADC) and single-quantum (SQ) and triple-quantum-filtered (TQF) sodium-23 ( ²³Na) magnetic resonance (MR) imaging. Materials and Methods: Sprague-Dawley rats (n = 8) were inoculated with 10⁶ N1-S1 cells. IA BR (20 mg/kg) was infused after 14 days. Animals were killed 1 day (n = 4) or 21 days (n = 4) after therapy. Imaging was performed 1 day before and after treatment. Volume was assessed over 2 weeks. Percentage apoptosis was counted from terminal deoxynucleotidyl transferase dUTP nick-end labeling-stained slides at 400×magnification. Kruskal-Wallis tests were used to compare apoptosis, and Wilcoxon signed-rank tests were used to compare MR signal intensity (SI). Results: Apoptosis was marginally greater in tumor than in nontumor (6.7% vs 1.3%; P =.08), varying from 2% to 10%. Before treatment, MR SI was greater in tumor than in nontumor (ADC, 1.18 vs 0.76 [P =.0078]; SQ, 1.20 vs 1.04 [P =.03]; TQF, 0.55 vs 0.34 [P =.03]). After treatment, tumors increased in volume (0.62 vs 0.33; P =.016) variably over 2 weeks. MR SI remained greater in tumor than in nontumor (ADC, 1.20 vs 0.77 [P =.0078]; SQ, 1.76 vs 1.15 [P =.016]; TQF, 0.84 vs 0.49 [P =.03]). SQ and TQF SI increased by 47% (P =.016) and 53% (P =.016) in tumors, whereas ADC did not change. Conclusions: Apoptosis was marginal and varied from 2% to 10%. Water ADC, SQ, and TQF MR imaging distinguished tumor from nontumor. Changes in water ADC and sodium MR imaging correlated to apoptosis and volume in select cases, but additional animals are needed to validate this trend against tumor growth.