使用 99mTc-MIBI SPECT/CT 成像在局部晚期乳腺癌中体内检测多药耐药相关蛋白：与临床结局的相关性。

In Vivo Detection of Multidrug-Resistance Related Proteins in Locally Advanced Breast Cancer Using 99mTc-MIBI SPECT/CT Imaging: Correlation with Clinical Outcomes.

机构信息

Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Assiut University, Egypt.

Department of Radiation Oncology and Nuclear Medicine, South Egypt cancer institute, Assuit University, Egypt.

出版信息

Asian Pac J Cancer Prev. 2024 Sep 1;25(9):3125-3141. doi: 10.31557/APJCP.2024.25.9.3125.

DOI:10.31557/APJCP.2024.25.9.3125

PMID:39342592

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11700319/

Abstract

OBJECTIVE

Neoadjuvant chemotherapy (NACT) is widely used for treating locally advanced Breast cancer (LABC). However, development of multidrug resistance (MDR) is the main underlying factor for chemoresistance. Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for MDR. This study aimed to analyze the relationship between expression of MDR-related proteins (P-gp and Bcl-2) and 99mTc-MIBI uptake and retention in BC tumor cells, pathologic response to NACT, disease free survival (DFS) and overall survival (OS).

METHODS

prospective analysis recruited 31 patients with LABC who received NACT between January 2019 and March 2020. 99mTc-MIBI planar and SPECT/CT imaging was conducted before and after NACT. Qualitative and quantitative analyses were performed, pre and post-NACT early and delayed lesion to non-lesion (LNL) ratios, and retention index (RI) of 99mTc-MIBI were calculated. Expression of P-gp and Bcl-2 in tumor cells was determined by immunohistochemistry.

RESULTS

Quantitively, inter-reader ICC for SPECT/CT based quantification was consistently higher than that of planar images. Post-NACT LNL ratios were significantly higher in patients with pathologic persistent disease (PPD). A change in RI between pre- and post-NACT scans demonstrated a significant association with DFS with a hazard ratio of 0.7 (95%CI: 06-1.0). Qualitatively, SPECT/CT was significantly more accurate compared to planar imaging in identifying residual viable tumor (81% compared to 57%). Her2neu positivity and high post-operative Bcl-2 and P-gp were associated with worse DFS. A significant association was found between increased expression of post-NACT Bcl-2 and PPD, advanced tumor stage and poor OS.

CONCLUSION

99mTc-MIBI SPECT/CT based qualitative evaluation of BC response to NACT is more accurate than planar imaging. Post-NACT MIBI retention is positively correlated with P-gp and Bcl-2 expression. 99mTc-MIBI SPECT/CT may predict MDR development. High post-NACT Bcl-2 expression is significantly associated with advanced tumor stage and OS. High post-NACT P-gp expression has a worse impact on pathologic response and DFS.

摘要

目的

新辅助化疗（NACT）广泛用于治疗局部晚期乳腺癌（LABC）。然而，多药耐药（MDR）的发展是化疗耐药的主要潜在因素。锝-99m 甲氧异丁基异腈（99mTc-MIBI）是 MDR 的底物。本研究旨在分析 MDR 相关蛋白（P-gp 和 Bcl-2）表达与乳腺癌肿瘤细胞 99mTc-MIBI 摄取和保留、NACT 病理反应、无病生存（DFS）和总生存（OS）之间的关系。

方法

前瞻性分析招募了 31 名 2019 年 1 月至 2020 年 3 月期间接受 NACT 的 LABC 患者。NACT 前后进行 99mTc-MIBI 平面和 SPECT/CT 成像。进行定性和定量分析，计算 NACT 前后早期和延迟病变与非病变（LNL）比值、99mTc-MIBI 保留指数（RI）。通过免疫组织化学测定肿瘤细胞中 P-gp 和 Bcl-2 的表达。

结果

定量分析中，SPECT/CT 基于定量的读者间 ICC 始终高于平面图像。病理持续性疾病（PPD）患者的 NACT 后 LNL 比值显著升高。NACT 前后 RI 的变化与 DFS 显著相关，风险比为 0.7（95%CI：0.6-1.0）。定性分析中，SPECT/CT 在识别残留存活肿瘤方面明显优于平面成像（81%比 57%）。Her2neu 阳性和术后高 Bcl-2 和 P-gp 与较差的 DFS 相关。NACT 后 Bcl-2 和 PPD 的表达增加与晚期肿瘤分期和不良 OS 显著相关。

结论

基于 99mTc-MIBI SPECT/CT 的 BC 对 NACT 的反应定性评估比平面成像更准确。NACT 后 MIBI 保留与 P-gp 和 Bcl-2 表达呈正相关。99mTc-MIBI SPECT/CT 可能预测 MDR 的发展。NACT 后高 Bcl-2 表达与晚期肿瘤分期和 OS 显著相关。NACT 后高 P-gp 表达对病理反应和 DFS 的影响更差。