Jacquier-Sarlin M R, Polla B S, Slosman D O
Department of Radiology, UFR Cochin, Paris, France.
J Nucl Med. 1996 Aug;37(8):1413-6.
Several clinical observations have suggested that HMPAO cerebral uptake might be related not only to regional cerebral perfusion but also to the nature of the lesion. Our aim was to investigate at the cellular level the nature of the process(es) involved in HMPAO accumulation in vitro.
Time-course incorporation of HM-PAO was studied in a fast-growing human premonocytic line, U937, in a human astrocytic-derived cell line, U373 and a human hybridized endothelial cell line, EaHy926. Minimal differences of HMPAO retention between these cell lines were observed and plateau of %U(HMPAO) (cpm cells/cpm standard of injected) were achieved within 2 hr. Because HMPAO cell retention was related to the intracellular content in glutathione, experiments studying effects of redox were conducted by preexposing U937 cells to D, L dithiothreitol or 2-Mercaptoethanol.
Overnight incubation with NAC or BSO did not significantly modified the kinetic of 99mTc-HMPAO incorporation while overnight incubation with NAC resulted in a 2-fold increase in intracellular glutathione content and overnight incubation with BSO nearly abolished the intracellular glutathione content. At the opposite, presence of these reducing agents in the medium during the experiments completely abolished 99mTc-HMPAO retention.
Our data thus provide in vitro evidence to support that overall intracellular retention of HMPAO is more dependent upon the redox activity of the tissue than the intracellular glutathione content. SPECT-HMPAO may accurately reflect regional cerebral blood flow in a normal state but possibly not in all pathological situations in which cell metabolism disturbances are characterized by alterations in the redox status.
多项临床观察表明，六甲基丙烯胺氧脑摄取不仅可能与局部脑灌注有关，还可能与病变的性质有关。我们的目的是在细胞水平上研究体外六甲基丙烯胺氧（HMPAO）蓄积所涉及的过程的性质。
在快速生长的人早幼单核细胞系U937、人星形胶质细胞衍生细胞系U373和人杂交内皮细胞系EaHy926中研究了HM-PAO的时间进程掺入情况。观察到这些细胞系之间HMPAO保留的差异极小，并且在2小时内达到了%U（HMPAO）（细胞计数/注射标准计数）的平台期。由于HMPAO细胞保留与谷胱甘肽的细胞内含量有关，因此通过将U937细胞预先暴露于D，L-二硫苏糖醇或2-巯基乙醇来进行研究氧化还原作用的实验。
用N-乙酰半胱氨酸（NAC）或丁硫氨酸亚砜胺（BSO）过夜孵育并未显著改变99mTc-HMPAO掺入的动力学，而用NAC过夜孵育导致细胞内谷胱甘肽含量增加2倍，用BSO过夜孵育几乎消除了细胞内谷胱甘肽含量。相反，在实验过程中培养基中存在这些还原剂完全消除了99mTc-HMPAO的保留。
因此，我们的数据提供了体外证据，支持HMPAO的总体细胞内保留更多地取决于组织的氧化还原活性而非细胞内谷胱甘肽含量。单光子发射计算机断层扫描（SPECT）-HMPAO可能在正常状态下准确反映局部脑血流量，但在所有以氧化还原状态改变为特征的细胞代谢紊乱的病理情况下可能并非如此。
