Preparation and preclinical evaluation of&nbsp; <sup>68</sup> Ga-P214 PSMA-targeting probe with SCN-Bn-DOTA as chelating group

DUAN Xiaojiang; ZHANG Zhuochen; FU Zijian; PAN Xingcan; YANG Xing

doi:10.19732/j.cnki.2096-6210.2024.04.004

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Preparation and preclinical evaluation of ⁶⁸ Ga-P214 PSMA-targeting probe with SCN-Bn-DOTA as chelating group

更新时间：2025-12-15

- Preparation and preclinical evaluation of ⁶⁸ Ga-P214 PSMA-targeting probe with SCN-Bn-DOTA as chelating group
- Vol. 33, Issue 4, Pages: 362-368(2024)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.19732/j.cnki.2096-6210.2024.04.004
  CLC：
- Published Online：12 September 2024，
  
  Published：12 September 2024
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段小江,张卓晨,傅子鉴,等. 以SCN-Bn-DOTA为螯合基团的PSMA靶向探针⁶⁸Ga-P214的制备与临床前评估[J]. 肿瘤影像学, 2024, 33(4): 362-368 https://doi.

org/10.19732/j.cnki.2096-6210.2024.04.004
段小江,张卓晨,傅子鉴,等. 以SCN-Bn-DOTA为螯合基团的PSMA靶向探针⁶⁸Ga-P214的制备与临床前评估[J]. 肿瘤影像学, 2024, 33(4): 362-368 https://doi. DOI： 10.19732/j.cnki.2096-6210.2024.04.004.

org/10.19732/j.cnki.2096-6210.2024.04.004 DOI：

摘要

目的：

适当延长三七素类前列腺特异性膜抗原（prostate specific membrane antigen，PSMA）靶向探针的体内循环时间，开发新型

Ga标记的前列腺癌诊断探针。

方法：

采用固相合成法制备配体P214（以p-SCN-Bn-DOTA为双功能螯合基团），测定其亲和性。将配体加入到含

离子的缓冲液中，95 ℃下反应5 min，纯化后使用放射性薄层色谱法测定其放射化学纯度。评估

Ga-P214的体外稳定性、脂水分配系数和人血清白蛋白结合率，并进行细胞摄取实验。对荷22Rv1瘤小鼠注射

Ga-P214，特定时间进行micro-正电子发射体层成像（positron emission tomography，PET）/计算机体层成像（computed tomography，CT）显像，并与

Ga-P137进行对比显像。尾静脉注射探针30、60和120 min后，处死实验鼠，取感兴趣器官称重、计数、计算每克组织注射剂量活度百分比（%ID/g）。

结果：

成功合成目标配体P214，其K i 值为0.085 nmol/L，标记产物

Ga-P214放射化学纯度大于95%，在生理盐水和37 ℃小鼠血清中2 h保持稳定。

Ga-P214的脂水分配系数为-3.17±0.09，对人血清白蛋白的结合率为（88.86±0.51）%，明显高于

Ga-P137的（74.01±1.17）%。细胞实验发现

Ga-P214能够有效被PSMA+细胞22Rv1摄取，温育30 、60和120 min后，细胞摄取分别为（0.39±0.14）、（0.55±0.09）、（0.54±0.12）%ID/10 5 细胞，且可被PSMA抑制剂ZJ43所抑制。注射后60 min，

Ga-P214在肿瘤区域内有更高的最大标准摄取值（maximum standard uptake value，SUV

max

）（1.40±0.11

0.80±0.04），且随时间而增加。荷瘤小鼠生物分布表明，

Ga-P214在肿瘤的摄取明显高于

-P137［（44.15±6.25）%ID/g

（19.76±3.56）%ID/g，注射后120min］，

Ga-P214拥有优异的肿瘤/肌肉、肿瘤/血液和肿瘤/肝脏的比值（127.63、33.87和12.68）。

结论：

Ga-P214生物分布理想，适当延长了三七素类探针的在体循环时间，在PSMA阳性肿瘤中的摄取显著增加，有望应用于前列腺癌的诊断，有较大的潜力改造为治疗探针。

Abstract

Objective:

To appropriately extend the in vivo circulation time of ginsenoside-like prostate-specific membrane antigen (PSMA) targeting probes and develop a novel

Ga-labeled diagnostic probe for prostate cancer.

Methods:

The ligand P214 (using p-SCN-Bn-DOTA as a bifunctional chelator) was synthesized using solid-phase synthesis

and its affinity was measured. The ligand was added to a buffer containing

ions

reacted at 95 ℃ for 5 min

and then purified. The radiochemical purity was determined using radioactive thin-layer chromatography. The in vitro stability

lipophilicity and human serum protein binding rate of

Ga-P214 were evaluated

followed by cell uptake experiments.

Ga-P214 was injected into 22Rv1 tumor-bearing mice

and micro-positron emission tomography (PET)/computed tomography (CT) imaging was performed at specific time points

with comparative imaging using

Ga-P137. Mice were sacrificed at 30

60 and 120 min post-injection via tail vein

and organs of interest were weighed

counted

and the percentage of injected dose per gram of tissue (%ID/g) was calculated.

Results:

The target ligand P214 was successfully synthesized with a K i value of 0.085 nmol/L

and the radiochemical purity exceeded 95%. The labeled product

Ga-P214 remained stable in saline and 37 ℃ mouse serum for 2 h. The lipophilicity (partition coefficient) of

Ga-P214 was -3.17±0.09

and the human serum albumin binding rate was (88.86±0.51)%

significantly higher than that of

Ga-P137 (74.01±1.17)%. Cell experiments demonstrated that

Ga-P214 was effectively taken up by PSMA+cells (22Rv1)

with uptake rates of (0.39±0.14)

(0.55±0.09)

and (0.54±0.12) %ID/10 5 cells at 30

and 120 min of incubation

respectively

which could be inhibited by the PSMA inhibitor ZJ43. At 60 min post-injection

Ga-P214 had a higher maximum standard uptake value (SUV

max

) in the tumor region (1.40±0.11

0.80±0.04)

which increased over time. Biodistribution in tumor-bearing mice showed that

Ga-P214 had significantly higher uptake in tumors compared to

Ga-P137 ［(44.15±6.25)%ID/g

(19.76±3.56)%ID/g at 120 min post-injection］

with superior tumor/muscle

tumor/blood

and tumor/liver ratios (127.63

33.87

and 12.68

respectively).

Conclusion:

Ga-P214 exhibits ideal biodistribution

appropriately extends the in vivo circulation time of ginsenoside-like probes

and significantly increases uptake in PSMA-positive tumors

making it a promising candidate for prostate cancer diagnosis with considerable potential to be developed into a therapeutic probe.

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Related Institution

Department of Nuclear Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University Cancer Research Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine

Department of Nuclear Medicine, Henan Cancer Hospital

Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Clinical Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences

Department of Nuclear Medicine, Affilitated Hospital of Southwest Medical University

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Preparation and preclinical evaluation of 68 Ga-P214 PSMA-targeting probe with SCN-Bn-DOTA as chelating group

DOI：10.19732/j.cnki.2096-6210.2024.04.004

摘要

Abstract

关键词

Keywords

references

Preparation and preclinical evaluation of ⁶⁸ Ga-P214 PSMA-targeting probe with SCN-Bn-DOTA as chelating group