Abstract

Purpose

The novel molecular imaging probe ^99mTc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer.

Methods

^99mTc-HYNIC-H10F was developed by labeling H10F peptide with ^99mTc following an optimized protocol. Biodistribution and SPECT/CT were performed in mouse models bearing HER2-positive SK-BR3 and HER2-negative MDA-MB-231 human breast cancer xenografts, respectively. The treatment response to trastuzumab was monitored and quantified by SPECT/CT in two HER2-positive breast cancer models (SK-BR3 and MDA-MB-361). The preliminary clinical study was performed in two patients with breast cancer.

Results

SPECT/CT with ^99mTc-HYNIC-H10F showed that the SK-BR3 tumors were clearly visualized, while the signals from MDA-MB-231 tumors were much lower. The tumor uptake of ^99mTc-HYNIC-H10F could be blocked by excess unlabeled H10F peptide but not by excess trastuzumab. The growth of two HER2-positive tumors was prominently suppressed at day 11 post-treatment. However, SPECT/CT reflected much earlier therapy response at day 4 post-treatment. The HER2 expression in tumors of breast cancer patients could be detected by ^99mTc-HYNIC-H10F SPECT/CT imaging.

Conclusions

^99mTc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, ^99mTc-HYNIC-H10F binds to a different domain of HER2 antigen, providing new opportunities to monitor HER2 expression levels before/during/after trastuzumab treatment for more effective personalized treatment.

中文翻译：

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在曲妥珠单抗治疗期间用肽探针99mTc-HYNIC-H10F成像和监测HER2在乳腺癌中的表达。

摘要

目的

开发了新型分子成像探针^99m Tc-HYNIC-H10F，用于通过SPECT成像对乳腺癌中HER2的表达进行曲妥珠单抗治疗的患者筛选和疗效监测。

方法

^99m Tc-HYNIC-H10F是通过按照优化方案用^99m Tc标记H10F肽而开发的。生物分布和SPECT / CT分别在带有HER2阳性SK-BR3和HER2阴性MDA-MB-231人乳腺癌异种移植物的小鼠模型中进行。在两种HER2阳性乳腺癌模型（SK-BR3和MDA-MB-361）中，通过SPECT / CT监测并量化了对曲妥珠单抗的治疗反应。初步临床研究在两名乳腺癌患者中进行。

结果

带有^99m Tc-HYNIC-H10F的SPECT / CT显示SK-BR3肿瘤清晰可见，而MDA-MB-231肿瘤的信号低得多。过量的未标记H10F肽可以阻止^99m Tc-HYNIC-H10F的肿瘤摄取，但过量的曲妥珠单抗则不能阻止其摄取。在治疗后第11天，两个HER2阳性肿瘤的生长受到显着抑制。但是，SPECT / CT在治疗后第4天反映了较早的治疗反应。通过^99m Tc-HYNIC-H10F SPECT / CT成像可以检测出乳腺癌患者肿瘤中的HER2表达。

结论

^99m Tc-HYNIC-H10F专门积聚在HER2阳性肿瘤中。与曲妥珠单抗相比，^99m Tc-HYNIC-H10F与HER2抗原的不同结构域结合，为监视更有效的个性化治疗之前/期间/之后的HER2表达水平提供了新的机会。