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前列腺特异性膜抗原(PSMA)正电子发射断层扫描(PET)能否检测出原发性前列腺癌组织学PSMA表达中的肿瘤内异质性?对[镓(Ga)]Ga-PSMA-11和[氟(F)]PSMA-1007的分析

Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [Ga]Ga-PSMA-11 and [F]PSMA-1007.

作者信息

Waibel Philipp Moritz Adrian, Glavynskyi Ievgen, Fechter Tobias, Mix Michael, Kind Felix, Sigle August, Jilg Cordula Annette, Gratzke Christian, Werner Martin, Schilling Oliver, Bronsert Peter, Freitag Martin Thomas, Zamboglou Constantinos, Grosu Anca-Ligia, Spohn Simon Konrad Benedikt

机构信息

Department of Radiation Oncology, University Medical Centre Freiburg, Robert-Koch Straße 3, 79106, Freiburg, Germany.

Institute for Surgical Pathology, University Medical Centre Freiburg, Freiburg, Germany.

出版信息

Eur J Nucl Med Mol Imaging. 2025 May;52(6):2023-2033. doi: 10.1007/s00259-025-07078-5. Epub 2025 Jan 17.

Abstract

PURPOSE

Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [Ga]Ga-PSMA-11 or [F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.

METHODS

Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [Ga]Ga-PSMA-11 (cohort I, 20 patients) or [F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman's coefficients of PSMA expression to mean and maximum standardized uptake value (SUV and SUV) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed.

RESULTS

Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUV and SUV (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUV / SUV was found for tumour areas larger than 400 μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72).

CONCLUSION

PSMA PET with both [Ga]Ga-PSMA-11 or [F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.

摘要

目的

前列腺特异性膜抗原正电子发射断层扫描(PSMA PET)是对前列腺癌(PCa)进行非侵入性特征描述的一种有前景的方法。本研究评估了使用示踪剂[Ga]Ga-PSMA-11或[F]PSMA-1007的PET是否能够描绘组织学PSMA表达的肿瘤内异质性。

方法

前瞻性纳入35例经活检证实为原发性PCa且无转移疾病证据或既往未接受过干预的患者。所有患者均接受PSMA PET联合计算机断层扫描(CT),其中20例患者使用[Ga]Ga-PSMA-11(队列I),15例患者使用[F]PSMA-1007(队列II),随后进行根治性前列腺切除术。对标本进行离体CT扫描并进行组织学制备。在数字化的全层前列腺切片上,手动定义具有不同形态的PCa区域,并在人工智能(AI)辅助下计算免疫组织化学PSMA表达的H评分。将H评分相似的PCa区域在离体CT上进行统一分割。在PSMA PET-CT上进行配准后,计算PSMA表达与平均和最大标准化摄取值(SUV和SUV)的Spearman系数。此外,分析PSMA PET中配准后的肿瘤区域与大体肿瘤体积(GTV)的一致性。

结果

32例患者纳入最终分析。对于组织学PCa区域,免疫组织化学PSMA表达与SUV和SUV显著相关(p < 0.001,p = 0.001)。对于组织学上大于400μm²的肿瘤区域,发现H评分与SUV / SUV之间存在近似线性相关性(p < 0.001)。与PSMA表达极低的肿瘤区域相比,PSMA表达强的肿瘤区域在配准后的PSMA PET中与GTV的重叠明显更大(p < 0.01)。两个示踪剂队列之间未发现显著差异(p = 0.72)。

结论

使用[Ga]Ga-PSMA-11或[F]PSMA-1007的PSMA PET能够检测PCa病变内组织学PSMA表达的变化,从而实现生物靶向放疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fad/12014795/77a1989f6e0b/259_2025_7078_Fig1_HTML.jpg

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