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：2026-06-18

- 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：
- Online First：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. DOI: 10.19732/j.cnki.2096-6210.2024.04.004.

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. DOI：

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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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

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