Vaidyanathan Ganesan, Affleck Donna J, Alston Kevin L, Welsh Philip, Zalutsky Michael R
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
Nucl Med Commun. 2004 Sep;25(9):947-55. doi: 10.1097/00006231-200409000-00013.
A fluorine substituted derivative of meta-iodobenzylguanidine (MIBG), 4-fluoro-3-iodobenzylguanidine (FIBG), is retained in SK-N-SH human neuroblastoma cells in vitro to a higher degree than the MIBG.
To investigate whether the higher retention of FIBG is due to differences in the catabolic degradation of the two tracers, in vitro paired-label studies were performed using SK-N-SH cells.
No detectable amount of benzyl amines, benzoic acids or hippuran derivatives, potential catabolites of these tracers, were seen in either case. Even after 48 h, the cell culture supernatants contained exclusively intact I-MIBG and I-FIBG. In contrast, in some cases, HPLC analysis of cell lysates indicated the presence of a very polar compound(s) as the predominant species with smaller quantities of intact tracers. The per cent total radioactivity in the lysate at each time point that was associated with intact I-FIBG was (average [range]) 25.4% [20.3-30.5], 22.5% [19.3-25.6], and 18.8% [14.3-23.3], at 0 h, 24 h and 48 h, respectively. The corresponding values for I-MIBG were 24.3% [21.0-27.5], 19.1% [11.7-26.5] and 17.4% [14.6-20.1]. No significant amount of activity was associated with high molecular weight species for either halobenzylguanidine, indicating that protein binding was not a major factor.
间碘苄胍（MIBG）的一种氟取代衍生物，4-氟-3-碘苄胍（FIBG），在体外人SK-N-SH神经母细胞瘤细胞中的潴留程度高于MIBG。
为研究FIBG较高的潴留率是否归因于这两种示踪剂分解代谢的差异，使用SK-N-SH细胞进行了体外配对标记研究。
在两种情况下均未检测到这些示踪剂的潜在分解代谢产物苄胺、苯甲酸或马尿酸衍生物。即使在48小时后，细胞培养上清液中仅含有完整的I-MIBG和I-FIBG。相比之下，在某些情况下，细胞裂解物的高效液相色谱分析表明存在一种极性很强的化合物作为主要成分，而完整示踪剂的量较少。在0小时、24小时和48小时时，与完整I-FIBG相关的裂解物中总放射性百分比（平均值[范围]）分别为25.4%[20.3-30.5]、22.5%[19.3-25.6]和18.8%[14.3-23.3]。I-MIBG的相应值分别为24.3%[21.0-27.5]、19.1%[11.7-26.5]和17.4%[14.6-20.1]。两种卤代苄胍与高分子量物质相关的活性均无显著差异，表明蛋白质结合不是主要因素。
