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Effects of L-DOPA pre-loading on the uptake of boronophenylalanine using the F98 glioma and B16 melanoma models

机译:使用F98胶质瘤和B16黑色素瘤模型预加载L-DOPA对摄取硼酰苯丙氨酸的影响

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摘要

The present study was undertaken to evaluate the effects of L-DOPA pre-loading on the uptake of BPA using the F98 rat glioma and the murine B16 melanoma models. In vitro pretreatments of F98 glioma and B16 melanoma cells with L-DOPA, followed by exposure to BPA increased boron uptake, as determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES). Based on this, in vivo studies were initiated in F98 glioma bearing rats. Initially, the LDOPA dosing paradigm was evaluated. Maximum tumor boron uptake was observed following i.p. administration of L-DOPA (50 mg/kg) followed 24 hrs later by BPA (31.8 ± 8.9 vs. 17.2 ± 6.3 μg/g for BPA alone). Next, the effect of L-DOPA pre-loading as a function of the route of administration of BPA was evaluated in F98 glioma bearing rats. The greatest increase in uptake was seen following i.v. administration of BPA, while in contrast no significant increase was seen following intracarotid (i.c.) administration (38.6 ± 12.4 vs. 34.2 ± 10.9). Cellular localization of the F98 glioma, as determined by secondary ion mass spectrometry (SIMS) boron imaging revealed equivalent tumor boron concentrations following L-DOPA pre-loading. In vivo studies in B16 melanoma bearing mice showed equivalent tumor boron values in treated and untreated mice, suggesting that the effects of L-DOPA pre-loading may depend both on the histologic type of tumor and its anatomic site.
机译:进行本研究以使用F98大鼠神经胶质瘤和鼠B16黑色素瘤模型评估L-DOPA预加载对BPA摄取的影响。 L-DOPA对F98胶质瘤和B16黑色素瘤细胞进行体外预​​处理,然后通过BPA暴露可增加硼吸收,这是通过电感耦合等离子体发射光谱法(ICP-OES)确定的。基于此,在携带F98胶质瘤的大鼠中开始了体内研究。最初,对LDOPA剂量范例进行了评估。腹腔注射后最大的肿瘤硼摄取量。给予L-DOPA(50 mg / kg),然后24小时后给予BPA(单独的BPA为31.8±8.9对17.2±6.3μg/ g)。接下来,在荷有F98神经胶质瘤的大鼠中评估了L-DOPA预加载与BPA给药途径的关系。静脉注射后最大吸收量增加。 BPA给药,相反,颈内(i.c.)给药后未见明显增加(38.6±12.4 vs. 34.2±10.9)。通过二次离子质谱(SIMS)硼成像确定的F98胶质瘤的细胞定位显示,在预加载L-DOPA之后,肿瘤硼的浓度相当。在B16黑色素瘤荷瘤小鼠中的体内研究显示,在治疗和未治疗的小鼠中,肿瘤硼的含量相当,这表明L-DOPA预加载的作用可能取决于肿瘤的组织学类型及其解剖部位。

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