Miederer Matthias, Molatore Sara, Marinoni Ilaria, Perren Aurel, Spitzweg Christine, Reder Sybille, Wester Hans-Jürgen, Buck Andreas K, Schwaiger Markus, Pellegata Natalia S
Department of Nuclear Medicine, Johannes Gutenberg University of Mainz, Langenbeck Strasse 1, 55131 Mainz, Germany.
Int J Mol Imaging. 2011;2011:175352. doi: 10.1155/2011/175352. Epub 2011 Jun 8.
Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or (11)C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of (11)C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.
受MENX多肿瘤综合征影响的大鼠会发生嗜铬细胞瘤（100%）。嗜铬细胞瘤是罕见肿瘤，动物模型稀缺，因此人们对MENX大鼠感兴趣，以识别和临床前评估新型靶向治疗方法。此类研究的一个先决条件是对与MENX相关的嗜铬细胞瘤进行灵敏且非侵入性的检测。我们进行了正电子发射断层扫描（PET），以确定大鼠嗜铬细胞瘤是否能被临床实践中使用的示踪剂检测到，如68Ga - DOTATOC（生长抑素类似物）或（11）C - 羟基麻黄碱（HED，一种去甲肾上腺素类似物）。我们分析了4只患病大鼠和3只未患病大鼠。PET扫描结果与肿瘤的组织病理学和免疫表型、增殖指数以及编码生长抑素受体或去甲肾上腺素转运体的基因表达相关。我们观察到，患病动物肾上腺中68Ga - DOTATOC的平均标准摄取值（SUV）为23.3±3.9，显著高于对照大鼠（15.4±7.9；P = 0.03）。与对照组（0.7±0.1）相比，MENX患病动物中（11）C - HED的平均肿瘤与肝脏比值增加（1.6±0.5），甚至更显著（P = 0.0016）。在一个独特的动物模型中，描绘嗜铬细胞瘤生物学中两条重要途径的功能成像区分了患病动物和对照动物，从而为未来使用MENX大鼠进行临床前研究奠定了基础。
