在无胸腺小鼠人神经母细胞瘤异种移植模型中对间位-[211At] 砹苯甲胍的评估。

Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model.

作者信息

Vaidyanathan G, Friedman H S, Keir S T, Zalutsky M R

机构信息

Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Nucl Med Biol. 1996 Aug;23(6):851-6. doi: 10.1016/0969-8051(96)00115-1.

DOI:10.1016/0969-8051(96)00115-1

PMID:8940730

Abstract

A paired-label biodistribution was performed in athymic mice bearing SK-N-SH human neuroblastoma xenografts to compare the tissue uptake of meta-[211At]astatobenzylguanidine ([211At]MABG) and [131I]MIBG. Significantly higher (p < 0.05) uptake of [211At]MABG was seen in tumor (3.8 +/- 0.8% ID/g vs. 3.1 +/- 0.7% ID/g at 8 h) compared to [131I]MIBG. Desipramine reduced tumor uptake of [211At] MABG by 43%, suggesting that its accumulation was related to the specific uptake-1 mechanism. Higher uptake of [211At]MABG was also seen in normal tissue targets such as heart (6.0 +/- 0.9% ID/g vs. 4.5 +/- 0.8% ID/g at 8 h; p < 0.05). Pretreatment of mice with unlabeled MIBG increased tumor uptake of [211At]MABG by 1.5-fold while reducing uptake in heart and several other normal tissues. The vesicular uptake inhibitor tetrabenazine reduced heart uptake by 30% without reducing the tumor uptake. These results suggest such strategies might be useful for improving [211At]MABG tumor-to-normal tissue ratios.

摘要

在携带SK-N-SH人神经母细胞瘤异种移植瘤的无胸腺小鼠中进行了配对标记生物分布实验，以比较间位-[211At]阿替苯胍（[211At]MABG）和[131I]MIBG的组织摄取情况。与[131I]MIBG相比，在肿瘤中观察到[211At]MABG的摄取显著更高（p < 0.05）（8小时时为3.8 +/- 0.8% ID/g，而[131I]MIBG为3.1 +/- 0.7% ID/g）。地昔帕明使[211At]MABG的肿瘤摄取降低了43%，表明其积累与特异性摄取-1机制有关。在心脏等正常组织靶点中也观察到[211At]MABG的摄取更高（8小时时为6.0 +/- 0.9% ID/g，而[131I]MIBG为4.5 +/- 0.8% ID/g；p < 0.05）。用未标记的MIBG预处理小鼠可使[211At]MABG的肿瘤摄取增加1.5倍，同时降低心脏和其他几种正常组织中的摄取。囊泡摄取抑制剂丁苯那嗪使心脏摄取降低了30%，而不降低肿瘤摄取。这些结果表明，此类策略可能有助于提高[211At]MABG的肿瘤与正常组织比值。