Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
Department of Nuclear Medicine, University Hospital of Würzburg, Würzburg, Germany.
Theranostics. 2022 Aug 8;12(13):5986-5994. doi: 10.7150/thno.75847. eCollection 2022.
Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic Ga-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. Eighty-seven MM patients underwent molecular imaging with Ga-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUV) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. Ga-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by Ga-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUVSpleen 4.06 ± 1.43 vs. 6.02 ± 1.16 vs. 7.33 ± 1.40; 0.001). Moreover, reduced splenic Ga-Pentixafor uptake was linked to unfavorable clinical outcome. Patients with a low SUVSpleen (<3.35) experienced a significantly shorter overall survival of 5 months as compared to 62 months in patients with a high SUVSpleen >5.79 ( 0.001). Multivariate Cox analysis confirmed SUVSpleen as an independent predictor of survival (HR 0.75; 0.009). These data suggest that splenic Ga-Pentixafor uptake might provide prognostic information in pre-treated MM patients similar to what was reported for diffusion-weighted magnetic resonance imaging. Further research to elucidate the underlying biologic implications is warranted.
除了是人类癌症中肿瘤生长和转移的关键因素外，C-X-C 基序趋化因子受体 4（CXCR4）也在许多免疫细胞中高度表达，允许对炎症活性进行非侵入性读出。最近的两项研究报告了浆细胞瘤疾病患者弥散加权磁共振成像中脾脏信号的预后意义，本研究旨在将多发性骨髓瘤（MM）中脾脏 Ga-Pentixafor 摄取与临床参数相关联，并评估其预后影响。87 例 MM 患者接受了 Ga-Pentixafor-PET/CT 分子成像。通过峰值标准化摄取值（SUV）和相应的脾脏/血池比值（TBR）半定量评估脾脏 CXCR4 表达，并与临床和预后特征以及生存参数相关联。所有 MM 患者的 Ga-Pentixafor-PET/CT 均为阳性，脾脏示踪剂摄取呈明显异质性。与对照或未经治疗的冒烟型多发性骨髓瘤患者相比，Ga-Pentixafor-PET/CT 确定的 CXCR4 表达与晚期疾病相关，并且与先前治疗线的数量呈负相关（SpleenSUV 4.06 ± 1.43 与 6.02 ± 1.16 与 7.33 ± 1.40；0.001）。此外，脾脏 Ga-Pentixafor 摄取减少与不良临床结局相关。与高 SUV 脾脏（>5.79）患者相比，低 SUV 脾脏（<3.35）患者的总生存显著更短，为 5 个月（0.001）。多变量 Cox 分析证实 SUV 脾脏是生存的独立预测因子（HR 0.75；0.009）。这些数据表明，脾脏 Ga-Pentixafor 摄取可能为预处理 MM 患者提供预后信息，类似于弥散加权磁共振成像报告的信息。需要进一步研究阐明潜在的生物学意义。
