Vaidyanathan Ganesan, Shankar Sriram, Affleck Donna J, Alston Kevin, Norman Joseph, Welsh Philip, LeGrand Holly, Zalutsky Michael R
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
Bioorg Med Chem. 2004 Apr 1;12(7):1649-56. doi: 10.1016/j.bmc.2004.01.026.
Radioiodinated meta-iodobenzylguanidine (MIBG) is used in the diagnosis and therapy of various neuroendocrine tumors. To investigate whether an additional guanidine function in the structure of MIBG will yield analogues that may potentially enhance tumor-to-target ratios, two derivatives-one with a guanidine moiety and another with a guanidinomethyl group at the 4-position of MIBG-were prepared. In the absence of any uptake-1 inhibiting conditions, the uptake of 4-guanidinomethyl-3-[(131)I]iodobenzylguanidine ([(131)I]GMIBG) by SK-N-SH cells in vitro was 1.7+/-0.1% of input counts, compared to a value of 40.3+/-1.4% for [(125)I[MIBG suggesting that guanidinomethyl group at the 4-position negated the biological properties of MIBG. On the other hand, 4-guanidino-3-[(131)I]iodobenzylguanidine ([(131)I]GIBG) had an uptake (5.6+/-0.3%) that was 12-13% that of [(125)I]MIBG (46.1+/-2.7%), and the ratio of uptake by control over DMI-treated (nonspecific) cultures was higher for [(131)I]GIBG (20.9+/-0.3) than [(125)I]MIBG itself (15.0+/-2.7). The exocytosis of [(131)I]GIBG and [(125)I]MIBG from SK-N-SH cells was similar. The uptake of [(131)I]GIBG in the mouse target tissues, heart and adrenals, as well as in a number of other tissues was about half that of [(125)I]MIBG. These results suggest that substitution of guanidine functions, especially a guanidinomethyl group, in MIBG structure may not be advantageous.
放射性碘化间碘苄胍（MIBG）用于多种神经内分泌肿瘤的诊断和治疗。为了研究在MIBG结构中增加胍功能是否会产生可能提高肿瘤与靶组织摄取比的类似物，制备了两种衍生物——一种在MIBG的4位带有胍基部分，另一种在4位带有胍甲基。在不存在任何摄取-1抑制条件下，体外SK-N-SH细胞对4-胍甲基-3-[(131)I]碘苄胍（[(131)I]GMIBG）的摄取为输入计数的1.7±0.1%，而[(125)I]MIBG的值为40.3±1.4%，这表明4位的胍甲基消除了MIBG的生物学特性。另一方面，4-胍基-3-[(131)I]碘苄胍（[(131)I]GIBG）的摄取率（5.6±0.3%）是[(125)I]MIBG（46.1±2.7%）的12 - 13%，并且[(131)I]GIBG（20.9±0.3）在对照与DMI处理（非特异性）培养物中的摄取比高于[(125)I]MIBG本身（15.0±2.7）。[(131)I]GIBG和[(125)I]MIBG从SK-N-SH细胞的胞吐作用相似。[(131)I]GIBG在小鼠靶组织、心脏和肾上腺以及许多其他组织中的摄取约为[(125)I]MIBG的一半。这些结果表明，在MIBG结构中取代胍功能，尤其是胍甲基，可能并无益处。
