Rutgers M, Tytgat G A, Verwijs-Janssen M, Buitenhuis C, Voûte P A, Smets L A
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam.
Int J Cancer. 1993 May 8;54(2):290-5. doi: 10.1002/ijc.2910540221.
The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131I]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin-equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PC12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC12 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro-adrenergic target cells.
肾上腺髓质显像剂间碘苄胍（MIBG）可被多种神经外胚层起源的肿瘤摄取。因此，放射性碘化的[131I]MIBG越来越多地用于这些疾病的诊断和治疗。为了研究与[131I]MIBG治疗相关的血小板减少症的病因，我们比较了MIBG与血清素在人血小板中的摄取情况。[131I]MIBG对丙咪嗪敏感的特异性摄取比[3H]血清素慢得多，但经过长时间孵育后，观察到其摄取水平较高且与血清素相当。MIBG的积累在比血清素高10至100倍的浓度下达到饱和，并且血清素对血小板摄取和细胞内储存的亲和力远高于MIBG。相反，血清素在SK-N-SH神经母细胞瘤和PC12嗜铬细胞瘤细胞中未被神经肾上腺素摄取-1显著浓缩。氟伏沙明抑制PC12细胞中去甲肾上腺素和MIBG的摄取，类似于其对血小板中血清素摄取的抑制作用。然而，该药物抑制血小板转运MIBG的效果比抑制血清素的效果强100倍。结果表明，血小板摄取MIBG不是由神经肾上腺素摄取-1介导的，而是可能通过血清素转运系统进行。血小板对MIBG的浓缩效率至少与神经肾上腺素肿瘤细胞相同，因此具有损伤这些细胞或巨核细胞前体的（放射）生物学潜力。氟伏沙明可以在对其在神经肾上腺素靶细胞中积累影响最小的浓度下选择性阻断血小板对MIBG的摄取。
