Grunewald Catrin, Sauberer Michael, Filip Thomas, Wanek Thomas, Stanek Johann, Mairinger Severin, Rollet Sofia, Kudejova Petra, Langer Oliver, Schütz Christian, Blaickner Matthias, Kuntner Claudia
Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz, DE -55128, Germany.
Health and Environment Department, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.
Nucl Med Biol. 2017 Jan;44:83-89. doi: 10.1016/j.nucmedbio.2016.08.012. Epub 2016 Aug 29.
In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [B]L-BPA.
Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injected with [B]L-BPA with tissue samples analyzed by prompt gamma activation analysis (PGAA) or quantitative neutron capture radiography (QNCR). The impact of L-tyrosine, L-DOPA and L-BPA preloading on the tissue distribution of [F]FBPA and [B]L-BPA was evaluated and the pharmacokinetics of [F]FBPA investigated by compartment modeling.
We found a significant correlation between [F]FBPA and [B]L-BPA uptake in tumors and various organs as well as high accumulation levels in pancreas and kidneys as reported in previous studies. Tumor-to-liver ratios of [F]FBPA ranged from 1.2 to 1.5. Preloading did not increase the uptake of [F]FBPA or [B]L-BPA in any organ and compartment modeling showed no statistically significant differences in [F]FBPA tumor kinetics.
[F]FBPA-PET predicts [B]L-BPA concentration after amino acid preloading in HuH-7 hepatocellular carcinoma models. Preloading had no effect on tumor uptake of [F]FBPA.
Despite differences in chemical structure and administered dose [F]FBPA and [B]L-BPA demonstrate an equivalent biodistribution in a preclinical tumor model. IMPLICATIONS FOR PATIENT CARE: [F]FBPA-PET is suitable for treatment planning and dose calculations in BNCT applications for liver malignancies. However, alternative tracers with more favorable tumor-to-liver ratios should be investigated.
近年来，硼中子俘获疗法（BNCT）的体外应用已用于评估肝脏原发性肿瘤或肝转移瘤。这种高风险手术的一个前提条件是证明硼药物在肝脏恶性肿瘤中优先递送并具有高摄取率。在这项研究中，我们在一个临床前肿瘤模型中评估了通过正电子发射断层扫描（PET）测量的[F]FBPA组织分布是否能够预测[B]L-BPA的组织分布。
荷瘤小鼠（肝癌细胞系，HuH-7）要么接受[F]FBPA-PET扫描，随后使用伽马计数器测量提取器官中的放射性含量，要么注射[B]L-BPA，并通过瞬发伽马活化分析（PGAA）或定量中子俘获放射成像（QNCR）分析组织样本。评估了L-酪氨酸、L-多巴和L-BPA预负荷对[F]FBPA和[B]L-BPA组织分布的影响，并通过房室模型研究了[F]FBPA的药代动力学。
我们发现肿瘤和各个器官中[F]FBPA与[B]L-BPA摄取之间存在显著相关性，以及如先前研究所报道的胰腺和肾脏中的高蓄积水平。[F]FBPA的肿瘤与肝脏比值范围为1.2至1.5。预负荷并未增加任何器官中[F]FBPA或[B]L-BPA的摄取，并且房室模型显示[F]FBPA肿瘤动力学无统计学显著差异。
在HuH-7肝癌模型中，[F]FBPA-PET可预测氨基酸预负荷后[B]L-BPA的浓度。预负荷对[F]FBPA的肿瘤摄取没有影响。
尽管化学结构和给药剂量存在差异，但[F]FBPA和[B]L-BPA在临床前肿瘤模型中显示出等效的生物分布。对患者护理的意义：[F]FBPA-PET适用于肝脏恶性肿瘤BNCT应用中的治疗规划和剂量计算。然而，应研究具有更有利肿瘤与肝脏比值的替代示踪剂。
