Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland.
Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):1210-1218. doi: 10.1016/j.ijrobp.2018.02.170. Epub 2018 Mar 8.
Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of F-misonidazole (F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated F-MISO PET-MRI modulation after 3 months of neoadjuvant androgen deprivation therapy (nADT).
Eleven PCa patients with a Gleason score (GS) ≥ 8 underwent F-fluorocholine (F-FCH) PET-computed tomography at diagnosis and an F-MISO hybrid PET-MRI examination before nADT; a second F-MISO PET-MRI examination was acquired after 3 months of nADT for all patients but one who dropped out because of noncompliance with nADT. Immunohistochemistry for tissue hypoxia- and proliferation-related biomarkers (glucose transporter 1, carbonic anhydrase IX, vascular endothelial growth factor A, Ki-67, hypoxia-inducible factor 1 alpha, and epidermal growth factor receptor) was performed in lesions bearing the highest GS. We used nonparametric tests to assess (1) the presence of F-MISO-positive regions (tumor-to-background ratio [TBR] ≥ 1.4) at baseline; (2) the correlation between imaging parameters (PET tracer uptake, Prostate Imaging Reporting and Data System [PIRADS] scores, and dynamic contrast enhancement perfusion markers) at baseline; (3) the difference in immunohistochemistry staining between F-MISO-positive and -negative lesions; and (4) the changes in F-MISO PET-MRI after nADT.
Uptake of F-MISO was significant in 7 patients, being coincidental with the highest GS region in 5 of them. A significant correlation was found at baseline between GS and F-MISO TBR, between F-MISO TBR and MRI perfusion markers, between GS and F-FCH maximum standardized uptake value, between GS and PIRADS score, and between F-FCH maximum standardized uptake value and PIRADS score. No difference was found between F-MISO-positive and -negative biopsy specimens with respect to tissue biomarkers. The TBR of F-MISO diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.
PET imaging with F-MISO showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high-grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a reoxygenation effect of nADT.
肿瘤缺氧与前列腺癌（PCa）放射治疗后的放射抵抗和预后不良有关。在这项前瞻性初步研究中，我们评估了 F-单碘苯并咪唑（F-MISO）正电子发射断层扫描（PET）-磁共振成像（MRI）检测接受根治性放疗的高危 PCa 患者缺氧的能力，并评估了 3 个月新辅助去势治疗（nADT）后 F-MISO PET-MRI 的调制。
11 名 GS≥8 的 PCa 患者在诊断时接受 F-氟胆碱（F-FCH）PET-计算机断层扫描，在 nADT 前接受 F-MISO 混合 PET-MRI 检查；除 1 名因不遵守 nADT 而退出的患者外，所有患者在 nADT 后 3 个月接受第二次 F-MISO PET-MRI 检查。在具有最高 GS 的病变中进行与组织缺氧和增殖相关的生物标志物（葡萄糖转运蛋白 1、碳酸酐酶 IX、血管内皮生长因子 A、Ki-67、缺氧诱导因子 1α 和表皮生长因子受体）的免疫组织化学检测。我们使用非参数检验评估（1）基线时 F-MISO 阳性区域（肿瘤与背景比[TBR]≥1.4）的存在情况；（2）基线时成像参数（PET 示踪剂摄取、前列腺成像报告和数据系统[PIRADS]评分和动态对比增强灌注标志物）之间的相关性；（3）F-MISO 阳性和阴性病变之间免疫组织化学染色的差异；和（4）nADT 后的 F-MISO PET-MRI 变化。
7 名患者的 F-MISO 摄取明显，其中 5 名患者与最高 GS 区域吻合。基线时发现 GS 与 F-MISO TBR、F-MISO TBR 与 MRI 灌注标志物、GS 与 F-FCH 最大标准化摄取值、GS 与 PIRADS 评分以及 F-FCH 最大标准化摄取值与 PIRADS 评分之间存在显著相关性。F-MISO 阳性和阴性活检标本之间在组织生物标志物方面没有差异。仅在高级别病变和基线摄取显著的区域中，nADT 后 F-MISO 的 TBR 显著降低。
F-MISO 的 PET 成像显示 PCa 有不同程度的摄取，与较高的 GS 相关，在 nADT 后 3 个月，高级别病变的摄取明显降低。这些结果表明 PCa 中存在缺氧微环境和 nADT 的再氧化作用。
