Preparation and preliminary biological evaluation of [<sup>18</sup>F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe

XU Wei; YAN Junjie; PAN Donghui; LI Meng; WU Wei; YANG Min

doi:10.3724/j.0253-3219.2025.hjs.48.250184

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Preparation and preliminary biological evaluation of [¹⁸F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe

NUCLEAR CHEMISTRY, RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE | 更新时间：2025-11-27

- Preparation and preliminary biological evaluation of [¹⁸F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe
- NUCLEAR TECHNIQUES Vol. 48, Issue 11, Article number: 110302(2025)
- 作者机构：
  
  1.江南大学生命科学与健康工程学院无锡 214122
  2.江南大学化学与材料工程学院无锡 214122
  3.国家卫生健康委员会核医学重点实验室，江苏省分子核医学重点实验室，江苏省原子医学研究所无锡 214063
- 作者简介：
  
  XU Wei, male, born in 1984, graduated from Nanjing Tech University in 2010, doctoral student, focusing on molecular imaging
  YANG Min, E-mail: yangmin@jsinm.org
- 基金信息：
  
  National Natural Science Foundation of China(32371434)
- DOI：10.3724/j.0253-3219.2025.hjs.48.250184
  CLC： TL99
- Received：26 April 2025，
  
  Revised：2025-06-30，
  
  Published：15 November 2025
- 稿件说明：
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徐伟,严骏杰,潘栋辉等.Al¹⁸F标记白蛋白结合剂修饰的PARP靶向显像探针的制备及初步生物学评价[J].核技术,2025,48(11):110302.

XU Wei,YAN Junjie,PAN Donghui,et al.Preparation and preliminary biological evaluation of [¹⁸F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe[J].NUCLEAR TECHNIQUES,2025,48(11):110302.
徐伟,严骏杰,潘栋辉等.Al¹⁸F标记白蛋白结合剂修饰的PARP靶向显像探针的制备及初步生物学评价[J].核技术,2025,48(11):110302. DOI： 10.3724/j.0253-3219.2025.hjs.48.250184. CSTR： 32193.14.hjs.CN31-1342/TL.2025.48.250184.

XU Wei,YAN Junjie,PAN Donghui,et al.Preparation and preliminary biological evaluation of [¹⁸F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe[J].NUCLEAR TECHNIQUES,2025,48(11):110302. DOI： 10.3724/j.0253-3219.2025.hjs.48.250184. CSTR： 32193.14.hjs.CN31-1342/TL.2025.48.250184.

摘要

多聚腺苷二磷酸核糖聚合酶（Poly(ADP-ribose) Polymerase，PARP）是癌症治疗中的重要靶点，动态评估其表达水平是实现精准治疗的必要前提。本研究拟基于PARP抑制剂奥拉帕利（Olaparib）的母核，设计并合成一种偶联白蛋白结合剂的新型

F标记PARP靶向正电子发射型计算机断层（Positron Emission Computed Tomography，PET）显像探针［

F］AlF-NOTA-LA，并结合体外实验与荷瘤小鼠活体microPET显像对探针的显像性能进行评估。研究表明，［

F］AlF-NOTA-LA标记时间约15 min，标记产率为（49.2±2.5）%，比活度为3.14 GBq∙μmol

-1

，放射化学纯度大于99%，脂水分配系数log

为-1.1±0.013，体外稳定性好。60 min时，［

F］AlF-NOTA-LA在MDA-MB-453细胞的摄取为（3.83±0.26）%AD，显著高于在A549细胞中的摄取（1.89±0.12）%AD。microPET显像结果显示，MDA-MB-453荷瘤鼠肿瘤对探针的摄取在10 min时达到最大值为（5.31±0.20）%ID∙g

-1

，而A549荷瘤鼠及阻断组的最大摄取分别为（3.04±0.03）%ID∙g

-1

和（2.23±0.11）%ID∙g

-1

。临床前研究结果初步表明，该探针体内药代动力学特性较差，经过结构改造后期望具有作为PARP靶向PET显像探针的潜力。

Abstract

Background

Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment

and dynamic assessment of its expression level is essential for achieving precision therapy.

Purpose

This study aims to assess the feasibility of using a novel albumin-binding PARP-targeted PET imaging probe for detecting PARP expression levels.

Methods

Firstly

based on the core structure of the PARP inhibitor Olaparib

the precursor NOTA-LA was synthesized using 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl) phthalazin-1(2H)-one and 4-(4-iodophenyl) butanoic acid as starting materials. Then

the target imaging probe

[

]

AlF-NOTA-LA

was radiolabeled

via

the non-covalent [

]

AlF method

and the probe was then characterized by determining its radiolabeling yield

radiochemical purity

molar activity

partition coefficient

and

in vitro

stability. Finally

the imaging performance of [

]

AlF-NOTA-LA was evaluated through

in vitro

cell-based assays and

in vivo

microPET imaging studies in A549 and MDA-MB-453 tumor-bearing mice.

Results

The radiolabeling of [

]

AlF-NOTA-LA is completed in approximately 15 min

yielding a radiolabeling efficiency of (49.2±2.5)%

with radiochemical purity exceeding 99%

a molar activity of 3.14 GBq∙μmol

-1

a log

value of -1.1±0.013

and excellent in vitro stability. After 60 min

the cellular uptake of [

]

AlF-NOTA-LA in MDA-MB-453 cells is (3.83±0.26)%AD

significantly higher than that in A549 cells (1.89±0.12)%AD. MicroPET imaging reveals that in MDA-MB-453 tumor-bearing mice

the probe's tumor uptake peaks at 10 min

reaching a maximum value of (5.31±0.20)%ID∙g

-1

(percentage injected dose per gram of tissue). In contrast

A549 tumor-bearing mice and blocking group showed significantly lower peak uptakes of (3.04±0.03)%ID∙g

-1

and (2.23±0.11)%ID∙g

-1

respectively.

Conclusions

Preliminary preclinical findings in this study indicate that the probe exhibited suboptimal pharmacokin

etic properties

in vivo

. Following structural modifications

it is anticipated to have potential as a PARP-targeted PET imaging probe.

关键词

Keywords

references

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Preparation and preliminary biological evaluation of [18F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe

DOI：10.3724/j.0253-3219.2025.hjs.48.250184

摘要

Abstract

关键词

Keywords

references

Preparation and preliminary biological evaluation of [¹⁸F]AlF-labeled Albumin-binding agent modified PARP-targeted imaging probe