title: 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.
abstract: OBJECTIVE
  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 ((23)Na) magnetic resonance (MR) imaging.
  
  
  METHODS
  Sprague-Dawley rats (n = 8) were inoculated with 10(6) 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.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. axf227@case.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Faramarzalian
authors.forename: Gordon
authors.initials: G
authors.lastname: McLennan
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Bennett
authors.forename: Andriy
authors.initials: A
authors.lastname: Babsky
authors.forename: Navin
authors.initials: N
authors.lastname: Bansal
authors.forename: Michael
authors.initials: M
authors.lastname: Lieber
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonnac
authors.forename: Krystoff
authors.initials: K
authors.lastname: Pankiewicz
authors.forename: Hiremagalur N
authors.initials: HN
authors.lastname: Jayaram
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001834:Body Water / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009705:Nucleosides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012964:Sodium / Q000378:metabolism*; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D009705:Nucleosides; C076145:3-(1-deoxyribofuranosyl)benzamide; D012964:Sodium