Provost Claire, Prignon Aurélie, Cazes Alex, Combaret Valérie, Delattre Olivier, Janoueix-Lerosey Isabelle, Montravers Françoise, Talbot Jean-Noël
Positronic Molecular Imaging Laboratory LIMP, UMS028, Pierre and Marie Curie University, Paris, France
Positronic Molecular Imaging Laboratory LIMP, UMS028, Pierre and Marie Curie University, Paris, France.
Anticancer Res. 2016 Sep;36(9):4459-66. doi: 10.21873/anticanres.10990.
BACKGROUND/AIM: Somatostatine receptors subtype 2 (SSTR2) are regarded as a potential target in neuroblastoma (NB) for imaging and promising therapeutic approaches. The purpose of this study was to evaluate and compare the SSTR2 status by (68)Ga-[tetraxetan-D-Phe1, Tyr3]-octreotide ((68)Ga-DOTATOC) positron-emission tomography (PET) and the tumour metabolic activity by (18)F-fluorodeoxyglucose (FDG) PET in different experimental models of NB.
Three cell lines of human NB with different levels of expression of SSTR2 were grafted into nude mice. Animals were imaged with FDG and (68)Ga-DOTATOC and the maximum standardized uptake value (SUVmax) was determined to quantify tracer uptake. Ex vivo biodistribution of (68)Ga-DOTATOC and immunohistochemical analysis of NB xenografts were performed.
Compared with FDG, the SUVmax of (68)Ga-DOTATOC uptake by the tumour was lower but the ratio to background was higher; there was a strong positive correlation between SUVmax values observed with the two tracers (r(2)=0.65). Sorting the cell lines according to uptake of FDG or (68)Ga-DOTATOC, injected activity per gram of tissue, Ki67 index or expression of SSTR2 assessed visually led to the same classification.
(68)Ga-DOTATOC allows preclinical imaging of NB according to the intensity of the expression of SSTR2. In contrast with what has been reported for neuroendocrine tumours, in this NB model, the (68)Ga-DOTATOC uptake was positively correlated with FDG uptake and with Ki67 index, usual markers of tumour aggressiveness. If confirmed in humans, this result would favour a theranostic application of (68)Ga-DOTATOC in NB, even in advanced stages.
背景/目的：生长抑素受体2型（SSTR2）被视为神经母细胞瘤（NB）成像及有前景治疗方法的潜在靶点。本研究旨在通过（68）Ga-[四氮杂环十二烷四乙酸-D-苯丙氨酸1，酪氨酸3]-奥曲肽（（68）Ga-DOTATOC）正电子发射断层扫描（PET）评估和比较NB不同实验模型中的SSTR2状态，并通过（18）F-氟脱氧葡萄糖（FDG）PET评估肿瘤代谢活性。
将三种SSTR2表达水平不同的人NB细胞系接种到裸鼠体内。用FDG和（68）Ga-DOTATOC对动物进行成像，并测定最大标准化摄取值（SUVmax）以量化示踪剂摄取。进行了（68）Ga-DOTATOC的离体生物分布及NB异种移植瘤的免疫组化分析。
与FDG相比，肿瘤摄取（68）Ga-DOTATOC的SUVmax较低，但与背景的比值较高；两种示踪剂观察到的SUVmax值之间存在强正相关（r（2）=0.65）。根据FDG或（68）Ga-DOTATOC摄取、每克组织注射活性、Ki67指数或视觉评估的SSTR2表达对细胞系进行排序，得到相同的分类。
（68）Ga-DOTATOC可根据SSTR2表达强度对NB进行临床前成像。与神经内分泌肿瘤的报道相反，在该NB模型中，（68）Ga-DOTATOC摄取与FDG摄取及Ki67指数呈正相关，Ki67指数是肿瘤侵袭性的常用标志物。如果在人体中得到证实，这一结果将有利于（68）Ga-DOTATOC在NB中的诊疗应用，即使在晚期阶段。
