In vitro and in vivo evaluation of targeted probe&nbsp; 68 Ga-NOTA-376 constructed by non-site-specific labeling method for CLDN18.2

LIU Chang; CHEN Yan; LI Dapeng; YANG Zhi; ZHU Hua

doi:10.19732/j.cnki.2096-6210.2024.04.003

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In vitro and in vivo evaluation of targeted probe ⁶⁸ Ga-NOTA-376 constructed by non-site-specific labeling method for CLDN18.2

更新时间：2025-12-15

- In vitro and in vivo evaluation of targeted probe ⁶⁸ Ga-NOTA-376 constructed by non-site-specific labeling method for CLDN18.2
- Vol. 33, Issue 4, Pages: 355-361(2024)
- 作者机构：
  
  1. 北京工业大学材料科学与工程学院,北京,100124
  2. 贵州大学医学院,贵州,贵阳,550025
  3. 北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科，消化系肿瘤整合防治全国重点实验室，国家药品监督管理局放射性药物研究与评价重点实验室，恶性肿瘤发病机制及转化研究教育部重点实验室,北京,100142
- 作者简介：
- 基金信息：
- DOI：10.19732/j.cnki.2096-6210.2024.04.003
  CLC：
- Published Online：11 September 2024，
  
  Published：11 September 2024
- 稿件说明：
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刘畅,陈艳,李大鹏,等. 非定点方法构建的靶向CLDN18.2探针⁶⁸ Ga-NOTA-376的体内外性质评价[J]. 肿瘤影像学, 2024, 33(4): 355-361 https://doi.

org/10.19732/j.cnki.2096-6210.2024.04.003
刘畅,陈艳,李大鹏,等. 非定点方法构建的靶向CLDN18.2探针⁶⁸ Ga-NOTA-376的体内外性质评价[J]. 肿瘤影像学, 2024, 33(4): 355-361 https://doi. DOI： 10.19732/j.cnki.2096-6210.2024.04.003.

org/10.19732/j.cnki.2096-6210.2024.04.003 DOI：

摘要

目的：

以非定点标记的方法构建

Ga标记的靶向CLDN18.2的正电子发射体层成像（positron emission tomography，PET）探针

Ga-NOTA-376，并评价其体内外性质。

方法：

以p-SCN-Bn-NOTA为螯合剂，非定点偶联靶向CLDN18.2的纳米抗体376，得到前体NOTA-376，对偶联后的前体进行

Ga放射性标记。通过放射性薄层色谱法（Radio thin layer chromatography，Raio-TLC）测定探针的标记率、放射化学纯度及体外稳定性，并进行探针在人胃腺癌小鼠模型的micro-PET/计算机体层成像（computed tomography，CT）显像实验。

结果：

68 Ga-NOTA-376显示出高标记率（89.98±0.07）%、高放射化学纯度（97.67±0.02）%以及较高的比活度（16.69±6.60）GBq/μmol，并且在5%人血清白蛋白（human serum albumin，HSA）和磷酸盐缓冲溶液（phosphate buffered saline，PBS）中保持稳定。Micro-PET/CT结果表明探针在CLDN18.2阳性肿瘤中的最大标准摄取值（maximum standard uptake value，SUV

max

）显著高于CLDN18.2阴性肿瘤，4.0 h时CLDN18.2阳性肿瘤及CLDN18.2阴性肿瘤的SUV max 分别为9.08±0.33及1.92±0.32。

结论：

本研究以非定点标记的方法成功构建了靶向CLDN18.2探针

Ga-NOTA-376，标记率高，具有良好的稳定性及靶向性，是一种有潜力的PET探针，可用于CLDN18.2蛋白表达水平的检测。

Abstract

Objective:

To construct a positron emission tomography (PET) probe

Ga-NOTA-376

targeting CLDN18

.2 using a non-site-specific labeling method

and to evaluate its in vitro and in vivo properties.

Methods:

The chelating agent p-SCN-Bn-NOTA was used to non-site-specifically conjugate the nanobody 376 targeting CLDN18.2

resulting in the precursor NOTA-376

which was then radiolabeled with

Ga. The labeling efficiency

radiochemical purity

and in vitro stability of the probe were determined by radio- thin layer chromatography (Radio-TLC)

and micro-PET/ computed tomography (CT) imaging experiments were conducted in a nude mouse model of human gastric adenocarcinoma.

Results:

Ga-NOTA-376 demonstrated a high labeling yield (89.98±0.07) %

high radiochemical purity (97.67±0.02)% and high specific activity (16.69±6.60) GBq/μmol

and remained stable in 5% human serum albumin (HSA) and phosphate-buffered saline (PBS). Micro-PET/CT results indicated that the maximum standardized uptake value (SUV

max

) of the probe in CLDN18.2-positive tumors was significantly higher than in CLDN18.2-negative tumors. At 4.0 h

the SUV

max

of CLDN18.2- positive tumors and CLDN18.2-negative tumors were 9.08±0.33 and 1.92±0.32

respectively.

Conclusion:

This study successfully constructed a CLDN18.2-targeting probe

Ga-NOTA-376 using a non-site-specific labeling method

which showed high labeling efficiency

good stability

and targeting capability

making it a potential PET probe for the detection of CLDN18.2 protein expression levels.

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In vitro and in vivo evaluation of targeted probe 68 Ga-NOTA-376 constructed by non-site-specific labeling method for CLDN18.2

DOI：10.19732/j.cnki.2096-6210.2024.04.003

摘要

Abstract

关键词

Keywords

references

In vitro and in vivo evaluation of targeted probe ⁶⁸ Ga-NOTA-376 constructed by non-site-specific labeling method for CLDN18.2