Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein

Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein
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DOI:
10.1007/s002590050403
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发表时间:
1999-04-01
期刊:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
影响因子:
--
通讯作者:
Dierckx, RA
Dierckx, RA
中科院分区:
其他
文献类型:
--
作者:
De Moerloose, B;Van de Wiele, C;Dierckx, RA

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锝-99mSestamibi成像提供了一种非侵入性的方法来检测功能性P-糖蛋白(Pgp),多药耐药的主要原因之一,在人类恶性肿瘤的存在。Pgp在原发性神经母细胞瘤亚群中的临床作用已被认为是原癌基因MYCN无扩增。我们想评价Tc-99 m-sestamibi骨显像在筛查Pgp存在的神经嵴瘤中的有用性。在10例MYCN阴性的神经母细胞瘤、神经节神经母细胞瘤或神经节神经瘤患儿中,在初步诊断时进行了Tc-99 m-sestamibi成像。所有患者在静脉注射740 MBq/1.73 m(2)Tc-99 m-Sestamibi后20-30 min和3.5 -4 h进行平面显像,测定肿瘤与正常组织的比值以及洗脱率,并与体外流式细胞术分析Pgp表达和功能进行比较。用单克隆抗体4 E3和MRK 16对Pgp表达进行流式细胞术分析,并通过在不存在或存在Pgp抑制剂的情况下的罗丹明123摄取和流出来评价Pgp功能在10名患者中的9名中,我们发现肿瘤内Tc-99 m-sestamibi活性与背景活性相当,这可能提示Pgp的存在。除一名患者外,所有患者均通过流式细胞术证实了这一点。Tc-99 m-sestamibi增强被认为是在原发肿瘤和骨髓转移的10例患者之一,这一结果是一致的阴性Pgp状态。研究结果表明,Tc-99 m-sestamibi成像结果可能与无MYCN扩增的神经嵴肿瘤中功能性Pgp的存在相关。
Imaging with technetium-99m sestamibi offers a non-invasive approach to detect the presence of functional P-glycoprotein (Pgp), one of the major causes of multidrug resistance, in human malignancies. A clinical role for Pgp has been suggested in the subpopulation of primary neuroblastoma without amplification of the proto-oncogene MYCN. We wanted to evaluate the usefulness of Tc-99m-sestamibi scintigraphy in the screening of neural crest rumours for the presence of Pgp. In ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or ganglioneuroma, Tc-99m-sestamibi imaging was performed at initial diagnosis. All patients underwent planar imaging 20-30 min and 3,5-4, h after intravenous injection of 740 MBq/1.73 m(2) Tc-99m-sestamibi, Tumour to normal tissue ratios, as well as washout rates, were determined and compared with in vitro flow cytometric analysis of Pgp expression and function, Pgp expression was analysed flow cytometrically with the monoclonal antibodies 4E3 and MRK16 and Pgp function was evaluated by means of rhodamine 123 uptake and efflux either in the absence or in the presence of the Pgp inhibitor verapamil, In nine of ten patients, we found that the intratumoral Tc-99m-sestamibi activity was comparable to the background activity which might be suggestive of Pgp presence. This was confirmed flow cytometrically in all but one patient. Tc-99m-sestamibi enhancement was seen in the primary tumour and the bone marrow metastases of one of the ten patients, and this result was concordant with a negative Pgp status. The findings presented suggest that Tc-99m-sestamibi imaging results might correlate with the presence of functional Pgp in neural crest tumours without MYCN amplification.