使用微型PET/CT对具有诊疗和放射治疗潜力的聚乙二醇化⁶⁴Cu脂质体进行体内评估。
In vivo evaluation of PEGylated ⁶⁴Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT.
作者信息
Petersen Anncatrine Luisa, Henriksen Jonas Rosager, Binderup Tina, Elema Dennis Ringkjøbing, Rasmussen Palle Hedengran, Hag Anne Mette, Kjær Andreas, Andresen Thomas Lars
机构信息
Department of Micro- and Nanotechnology, Technical University of Denmark, Building 345, 2800, Lyngby, Denmark.
Center for Nanomedicine and Theranostics, Technical University of Denmark, 2800, Lyngby, Denmark.
出版信息
Eur J Nucl Med Mol Imaging. 2016 May;43(5):941-952. doi: 10.1007/s00259-015-3272-6. Epub 2015 Dec 8.
PURPOSE
The objective of this study was to evaluate the potential of PEGylated (64)Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated (177)Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model.
METHODS
Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and (64)Cu- and (177)Lu-loading efficiency. The tumor imaging potential of (64)Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The (64)Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of (177)Lu-liposomes.
RESULTS
High remote loading efficiency (>95 %) was obtained for both (64)Cu and (177)Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the (64)Cu-liposomes estimated an acceptable total effective dose of 3.3·10(-2) mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic (177)Lu-liposomes.
CONCLUSION
The overall preclinical profile of PEGylated (64)Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of (64)Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated (64)Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for (177)Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of (177)Lu-liposomes in animals before potential testing in man.
目的
本研究的目的是通过在人异种移植小鼠模型中的体内表征和剂量分析，评估聚乙二醇化（64）Cu脂质体在临床诊断正电子发射断层扫描（PET）成像中的潜力以及聚乙二醇化（177）Lu脂质体在肿瘤内放射治疗中的潜力。
方法
对含有5 mol%和10 mol%聚乙二醇的脂质体进行大小、电荷以及（64）Cu和（177）Lu负载效率的表征。使用PET成像，根据体内生物分布、肿瘤蓄积和肿瘤与肌肉（T/M）比值评估负载（64）Cu的脂质体的肿瘤成像潜力。通过使用OLINDA/EXM软件进行剂量分析，进一步评估聚乙二醇化脂质体在诊断和治疗应用中的潜力。使用（64）Cu脂质体作为生物替代物来估计（177）Lu脂质体的器官和肿瘤动力学。
结果
聚乙二醇化脂质体对（64）Cu和（177）Lu放射性核素均具有较高的远程负载效率（>95%），并且在储存以及在37°C下血清孵育24小时后，未观察到封装的放射性核素出现明显泄漏。通过PET成像评估，10 mol%聚乙二醇脂质体的肿瘤蓄积（6.2±0.2 %ID/g）高于5 mol%聚乙二醇脂质体。（64）Cu脂质体的剂量分析估计，患者诊断成像的可接受总有效剂量为3.3·10（-2）mSv/MBq。对于潜在的放射治疗用（177）Lu脂质体，估计肿瘤吸收剂量较高（114 mGy/MBq）。
结论
聚乙二醇化（64）Cu脂质体的整体临床前概况显示出作为一种新型PET诊疗示踪剂用于人体成像的巨大潜力。剂量分析结果预测，患者初始给予200 MBq的（64）Cu脂质体应该是可接受的。正在进行工作以在临床研究项目中验证聚乙二醇化（64）Cu脂质体的效用。对（177）Lu脂质体估计的高肿瘤吸收剂量（114 mGy/MBq）以及初步的剂量研究证明，在可能进行人体试验之前，有必要在动物中对（177）Lu脂质体进行进一步的治疗和剂量研究。
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