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高纤维母细胞激活蛋白表达在去势抵抗性前列腺癌中支持 FAPI-分子治疗学的应用。

High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics.

机构信息

Department of Urology, University of Duisburg-Essen, and German Cancer Consortium (DKTK), University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.

Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2021 Dec;49(1):385-389. doi: 10.1007/s00259-021-05423-y. Epub 2021 Jul 5.

Abstract

PURPOSE

To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [ Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC).

METHODS

Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [ Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed.

RESULTS

The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [ Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC.

CONCLUSION

Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.

摘要

目的

评估成纤维细胞激活蛋白(FAP)在前列腺癌(PC)不同临床阶段的表达情况,探讨其在去势抵抗性前列腺癌(CRPC)患者中的[Ga]Ga-FAPI-04 PET/CT 成像的应用价值。

方法

从 94 例处于不同 PC 阶段(原发性 PC、接受新辅助雄激素剥夺治疗的患者、CRPC 和神经内分泌 PC(NEPC))的前列腺组织中构建组织微阵列(TMA),并用抗 FAP 单克隆抗体进行染色。采用阳性像素计数算法(H-指数)比较各组之间 FAP 表达。此外,对 3 例晚期 CRPC 或 NEPC 男性进行[Ga]Ga-FAPI-04 PET/CT 检查,分析 PET 阳性情况。

结果

良性组织、原发性 PC、根治性前列腺切除术前新辅助雄激素剥夺治疗、CRPC 和 NEPC 的平均 H-指数分别为 0.018、0.031、0.042、0.076 和 0.051,表明随着疾病的进展 FAP 表达显著增加。这些发现与[Ga]Ga-FAPI-04 PET/CT 的结果一致,在晚期 CRPC 男性中具有高度阳性。

结论

FAP 组织表达增加支持在 CRPC 中使用 FAP 抑制剂(FAPI)分子治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/8712308/c712b3a186ca/259_2021_5423_Fig1_HTML.jpg

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