Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , China.
Beijing Capture Tech Co., Ltd. , Beijing 102413 , China.
ACS Appl Mater Interfaces. 2018 Dec 19;10(50):43387-43395. doi: 10.1021/acsami.8b14682. Epub 2018 Dec 5.
Boron neutron capture therapy (BNCT) induces high-energy radiation within cancer cells while avoiding damage to normal cells without uptake of BNCT drugs, which is holding great promise to provide excellent control over locally invasive malignant tumors. However, lack of quantitative imaging technique to determine local boron concentration has been a great challenge for nuclear physicians to apply accurate neutron irradiation during the treatment, which is a key factor that has limited BNCT's application in clinics. To meet this challenge, this study describes coating boronated porphyrins with a biocompatible poly(lactide- co-glycolide)-monomethoxy-poly(polyethylene-glycol) (PLGA-mPEG) micelle for selective tumor accumulation and reduced toxicity comparing with the previously reported boronated porphyrin drugs. Fluorescence imaging and positron emission tomography (PET) imaging were performed, unveiling the potential imaging properties of this boronated porphyrin nanocomplex (BPN) to locate tumor region and to determine tissue-localized boron concentration which facilitates treatment planning. By studying the pharmacokinetics of BPN with Cu-64 PET imaging, the treatment plan was adjusted from single bolus injection to multiple times of injections of smaller doses. As expected, high tumor uptake of boron (125.17 ± 13.54 ppm) was achieved with an extraordinarily high tumor to normal tissue ratio: tumors to liver, muscle, fat, and blood were 3.24 ± 0.22, 61.46 ± 20.26, 31.55 ± 10.30, and 33.85 ± 5.73, respectively. At last, neutron irradiation with BPN showed almost complete tumor suppression, demonstrating that BPN holds a great potential for being an efficient boron delivery agent for imaging-guided BNCT.
硼中子俘获治疗（BNCT）在没有 BNCT 药物摄取的情况下，诱导癌细胞内产生高能辐射，同时避免对正常细胞造成损伤，这为精确控制局部侵袭性恶性肿瘤提供了很大的希望。然而，缺乏定量成像技术来确定局部硼浓度，这一直是核医学医生在治疗中进行精确中子照射的一大挑战，这也是限制 BNCT 在临床应用的关键因素。为了应对这一挑战，本研究描述了用生物相容性的聚（乳酸-共-乙醇酸）-单甲氧基-聚（聚乙二醇）（PLGA-mPEG）胶束对硼化卟啉进行包覆，以实现与先前报道的硼化卟啉药物相比的选择性肿瘤积累和降低毒性。进行了荧光成像和正电子发射断层扫描（PET）成像，揭示了这种硼化卟啉纳米复合物（BPN）定位肿瘤区域和确定组织局部硼浓度的潜在成像特性，从而有利于治疗计划的制定。通过使用 Cu-64 PET 成像研究 BPN 的药代动力学，治疗计划从单次推注调整为多次小剂量注射。正如预期的那样，实现了硼的高肿瘤摄取（125.17±13.54 ppm），肿瘤与正常组织的比值非常高：肿瘤与肝、肌肉、脂肪和血液的比值分别为 3.24±0.22、61.46±20.26、31.55±10.30 和 33.85±5.73。最后，用 BPN 进行中子照射几乎完全抑制了肿瘤，表明 BPN 具有成为用于成像引导 BNCT 的高效硼递药载体的巨大潜力。
