A Babsky, Ju Shenghong - Apparent diffusion coefficient of waterin evaluation of treatment response in animal body tumors - страница 4

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Одержано: 19.01.2009

Біологічні Студії / Studia Biologica • 2009 • Том 3/№1 С. 3-24

[1] tumors [61] and with the decrease in tumor cell density in 9L glioma [62]. 5FU-treat-ment of RIF-1 tumors also led to increase in ECS. The ratio of necrotic to total tumor area in histological sections was 52% higher than to controls three days after the treat­ment. Furthermore, cellular density was 26% lower in necrotic areas of the treated tu­mors [42]. In necrotic areas of tumors, much evidence of apoptotic and necrotic change was found, such as dusting nuclei, pyknosis, neutrophil invasion, and/or karyorrhexis.

Thoeny et al. used a rhabdomyosarcoma tumor model to study the effects of the vascular targeting agent combretastatin A4 on waterADC using a 1.5 T MR system [19, 43, 49]. Combretastatin A4 produces a reversible disruption of the vascular network in tumors causing cell death without damaging the vasculature of normal organs [63]. The authors proposed that the difference between the ADC values calculated using low b-values of 0, 50, and 100 s/mm2 (ADClow) and high b-values of 500, 750, and 1,000 s/mm2 (ADChi h) provides information about the perfusion component in ADC (ADCperf) [49]. They showed that treatment of sc-implanted rhabdomyosarcoma with a singlePip dose of 25 mg/kg combretastatin A4 leads to significant decreases in ADClow, ADChigh, and ADCperf 1 and 6 hr post-treatment and is associated with tumor growth delay. However, two and nine days after combrestatin A4 injection when the tumor growth delay turned up to significant growth, ADClowand ADChigh started to increase overlapping the before treatment values. ADCperfwas still lower on day 2 but increased on day 9 compared to the before treatment value. The changes in ADCperf were correlated with the volume transfer constant k (R2 = 0.46) and the initial slope (R2 = 0.67) calculated from perfusion data using dynamic contrast-enhanced MRI. The changes of mean ADC from the entire rhabdomyosarcoma showed similar trend to the ADChi h changes [19]. Thus, total tumor ADC showed an early decrease after combretastatin A4 injection from 1.26x10-3 mm2/s (before) to 1.18x10-3 mm2/s (1 hr) and 1.08x10-3 mm2/s (6 hr), histologically correspon­ding to vessel congestion and vascular shutdown in periphery but no necrosis. An in­crease of total tumor ADC (1.79x10-3 mm2/s) 2 days after the drug injection was associ­ated with progressive necrosis and a significant decrease 9 days after treatment (1.41x10-3 mm2/s) corresponded to tumor re-growth. Repeated combretastatin A4 ad­ministration at a dose of 25 mg/kg injected with an interval period of nine days retains efficacy in rat rhabdomyosarcomas, with similar effects on waterADC after each drug administration [43]. The authors concluded that both DW and dynamic contrast-en­hanced MRIs provide information about intratumoral cell viability and necrosis and allow monitoring of perfusion changes after administration ofvascular targeting agents.

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