Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
NMR Biomed. 2012 Apr;25(4):632-42. doi: 10.1002/nbm.1779. Epub 2011 Oct 24.
Magnetic resonance imaging (MRI) and spectroscopy (MRS) offer powerful approaches for detecting physiological and metabolic alterations in malignancies and help investigate underlying molecular mechanisms. Research on epithelial ovarian carcinoma (EOC), the gynaecological malignancy with the highest death rate characterised by frequent relapse and onset of drug resistance, could benefit from application of these molecular imaging approaches. In this study, MRI/MRS were used to characterise solid tumour models obtained by subcutaneous (s.c.) or intraperitoneal (i.p.) implantation of human SKOV3.ip cells in severe combined immunodeficiency (SCID) mice. In vivo MRI/MRS, ex vivo magic-angle-spinning (MAS), and in vitro (1)H-NMR measurements were carried out at 4.7 T, 9.4 T, and 9.4/16.5 T, respectively. MRI evaluation was performed by T1-, T2-, and diffusion-weighted (DW) multislice spin-echo imaging. The in vivo (1)H spectra of all tumour models showed a prominent resonance of total choline-containing metabolites (tCho). Quantitative in vivo MRS of both i.p. and s.c. SKOV3.ip xenografts showed that the mean tCho content was in the 2.9-4.5 mM range, with a mean PCho/tCho ratio of 0.99 ± 0.01 [23 examinations, 14-34 days post injection (dpi)], in good agreement with ex vivo and in vitro analyses. Myo-inositol ranged between 11.7 and 17.0 mM, with a trend towards higher values in i.p. xenografts at 14-16 dpi. The average apparent diffusion coefficient (ADC) values of SKOV3.ip xenografts [1.64 ± 0.11 (n = 9, i.p.) and 1.58 ± 0.03 x10(-3) mm(2)/s (n = 7, s.c.)] were in agreement with values reported for tumours from patients with EOC, while the mean vascular signal fraction (VSF) was lower (≤ 4%), probably due to the more rapid growth of preclinical models. Both s.c. and i.p. xenografts are valuable preclinical models for monitoring biochemical and physiopathological changes associated with in vivo EOC tumour growth and response to therapy, which may serve as the basis for further clinical development of noninvasive MR approaches.
磁共振成像（MRI）和波谱（MRS）为检测恶性肿瘤中的生理和代谢变化提供了强大的方法，并有助于研究潜在的分子机制。研究上皮性卵巢癌（EOC），这种妇科恶性肿瘤死亡率最高，其特征是经常复发和出现耐药性，可以受益于这些分子成像方法的应用。在这项研究中，我们使用 MRI/MRS 来描述通过皮下（s.c.）或腹腔内（i.p.）植入人 SKOV3.ip 细胞在严重联合免疫缺陷（SCID）小鼠中获得的实体瘤模型。在体 MRI/MRS、体外魔角旋转（MAS）和体外（1）H-NMR 测量分别在 4.7T、9.4T 和 9.4/16.5T 下进行。MRI 评估通过 T1-、T2-和扩散加权（DW）多切片自旋回波成像进行。所有肿瘤模型的体内（1）H 谱均显示总胆碱代谢物（tCho）的突出共振。对 i.p.和 s.c. SKOV3.ip 异种移植的定量体内 MRS 显示，tCho 含量的平均值在 2.9-4.5mM 范围内，PCho/tCho 比值的平均值为 0.99±0.01[23 次检查，注射后 14-34 天（dpi）]，与体外和体外分析结果一致。肌醇在 11.7 和 17.0mM 之间，在 14-16dpi 时 i.p.异种移植中呈上升趋势。SKOV3.ip 异种移植的平均表观扩散系数（ADC）值[1.64±0.11（n=9，i.p.）和 1.58±0.03 x10（-3）mm（2）/s（n=7，s.c.）]与报告的 EOC 患者肿瘤值一致，而平均血管信号分数（VSF）较低（≤4%），可能是由于临床前模型的生长速度较快。s.c.和 i.p.异种移植是监测与体内 EOC 肿瘤生长和对治疗反应相关的生化和生理病理变化的有价值的临床前模型，可为进一步开发非侵入性 MR 方法提供基础。
