钪-44放射性标记纳米体作为PD-L1 PET成像探针的合成及体外评价。

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Viktoria E Krol, Aditya Bansal, Manasa Kethamreddy, Jason R Ellinghuysen, Daniel J Vail, Fabrice Lucien-Matteoni, Haidong Dong, Sean S Park, Mukesh K Pandey
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引用次数: 0

摘要

背景/目的:基于无创PET成像的PD-L1表达评估对PD-L1免疫疗法的更好患者选择和治疗反应率具有很高的临床价值。由于其较短的生物半衰期和更快的清除血液池,放射性标记抗体片段是一个有吸引力的替代成像比他们的全长IgG对应。这项工作研究了用44Sc (t1/2 = 4.04 h)放射性标记的抗pd - l1 - b11纳米体的放射性合成和体外细胞摄取,作为抗pd - l1 - b11 - igg的替代品,更适合于半衰期较长的放射性同位素,如89Zr (t1/2 = 78.41 h)。方法:将蛋白质与p-SCN-Bn-DTPA结合,在室温下用44Sc进行放射标记,纯化前[44Sc]Sc-B11-IgG的放射化学产率为94.8±3.1% (n = 3), [44Sc] sc - b11 -纳米体的放射化学产率为73.6±12.1% (n = 3)。结果:两种探针在PD-L1+细胞中的摄取明显高于PD-L1 - ko细胞。然而,也观察到高非特异性摄取,特别是放射性标记的b11纳米体,这可能会对其作为分子成像探针的潜力产生负面影响。结论:由于44Sc在体外的高非特异性摄取,放射性标记纳米体没有进行进一步的体内评价。然而,这些结果不应该阻碍未来对其他基于纳米体的44Sc放射性标记探针的评估,因为它们的生物和物理半衰期非常匹配。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and In Vitro Evaluation of a Scandium-44 Radiolabeled Nanobody as a PD-L1 PET Imaging Probe.

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.

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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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