99m Tc-(EDDA/tricine)-HYNIC-GnRH analogue as a potential imaging probe for diagnosis of prostate cancer.,Chemical Biology & Drug Design

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99m Tc-(EDDA/tricine)-HYNIC-GnRH analogue as a potential imaging probe for diagnosis of prostate cancer.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2020-04-12 , DOI: 10.1111/cbdd.13693
Arezou Masteri Farahani _{1,

2} , Fariba Maleki _{1,

2} , Nourollah Sadeghzadeh ₁ , Saeid Abediankenari ₃ , Seyed Mohammad Abedi ₄ , Mostafa Erfani ₅

Affiliation

Prostate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by ^99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The K_d values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of ^99mTc‐HYNIC‐Ahx‐[DLys⁶]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using ^99mTc‐[DLys⁶]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of ^99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys⁶]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.

中文翻译：

99m Tc-（EDDA / tricine）-HYNIC-GnRH类似物作为诊断前列腺癌的潜在成像探针。

前列腺癌是对男性健康的严重威胁，因此有必要开发用于早期发现这种恶性肿瘤的技术。放射性标记的肽是诊断前列腺癌的有用工具。在这项研究中，我们设计了一种新的结合HYNIC的GnRH类似物，并在^99m Tc上用曲辛/ EDDA作为大肠菌素标记。我们使用氨基己酸（Ahx）作为碳氢化合物接头，以生成^99m Tc-（tricine / EDDA）-HYNIC-Ahx- [DLys ⁶ ] GnRH。放射性肽在溶液和血清中显示出高放射化学纯度和稳定性。两种人类前列腺癌细胞系LN-CaP和DU-145用于细胞实验。放射性肽对LN-CaP的结合特异性和亲和力优于DU-145细胞。该ķ _dLN-CaP和DU-145电池的值分别为41.91±7.03 nM和55.96±10.56 nM。肾脏高摄取证明放射性肽的主要排泄途径是通过泌尿系统。在LN-CaP异种移植裸鼠中，^99m Tc-HYNIC-Ahx- [DLys ⁶ ] GnRH的肿瘤/肌肉比在pi 1小时时为4.14，在pi 4 h时降至2.41。阻断实验表明肿瘤吸收是受体介导的。在感染后1小时，使用^99m Tc- [DLys ⁶ ] GnRH可以清晰地看到病变，因此，本研究着重介绍了^99m Tc-（tricine / EDDA）-HYNIC-Ahx- [DLys ⁶ ] GnRH肽作为有希望的药物的能力。表达GnRHR的肿瘤影像。

更新日期：2020-04-12

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