Herhaus Peter, Habringer Stefan, Vag Tibor, Steiger Katja, Slotta-Huspenina Julia, Gerngroß Carlos, Wiestler Benedikt, Wester Hans-Jürgen, Schwaiger Markus, Keller Ulrich
Internal Medicine III, Technische Universität München, Ismaningerstraße 22, Munich, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
EJNMMI Res. 2017 Dec;7(1):51. doi: 10.1186/s13550-017-0294-z. Epub 2017 Jun 2.
CXCR4 belongs to the family of chemokine receptors. Together with its sole known ligand CXCL12 (SDF-1alpha), it has a pivotal role during organogenesis and for homing of hematopoietic stem cells. CXCR4 is overexpressed in various malignancies, and this is often associated with poor prognosis. Therefore, molecular imaging of CXCR4 bears a great potential for diagnostics and selecting patients for CXCR4-directed therapies. The CXCR4-directed positron emission tomography (PET) tracer [Ga]Pentixafor has been shown to visualize CXCR4 expression in various malignancies in vivo. Whereas this tracer has limitations compared to F-Fluorodeoxyglucose ([F]FDG) in diagnostic PET imaging in peripheral tumour lesions, it might add valuable information in routine diagnostics and response assessment of tumours in close proximity to the central nervous system (CNS) and malignancies within this organ. As a proof-of-concept, we performed [Ga]Pentixafor PET imaging in a patient with extranodal marginal zone lymphoma (MZL) of the orbital cavities at diagnosis and for post-therapy response assessment. Compared to routinely conducted [F]FDG PET, the lymphoma lesions determined by magnetic resonance imaging (MRI) showed high tracer accumulation at diagnosis, which decreased upon treatment. We therefore propose that imaging of CXCR4 with [Ga]Pentixafor is a potential diagnostic tool for tumours close to or within the CNS and suggest this being studied in clinical trials.
CXCR4属于趋化因子受体家族。它与其唯一已知的配体CXCL12（基质细胞衍生因子-1α）一起，在器官发生过程以及造血干细胞归巢中发挥关键作用。CXCR4在多种恶性肿瘤中过度表达，这通常与预后不良相关。因此，CXCR4的分子成像在诊断以及为CXCR4导向治疗选择患者方面具有巨大潜力。CXCR4导向的正电子发射断层扫描（PET）示踪剂[镓]喷替沙福已被证明可在体内显示多种恶性肿瘤中CXCR4的表达。虽然与氟代脱氧葡萄糖（[F]FDG）相比，这种示踪剂在外周肿瘤病变的诊断性PET成像中存在局限性，但它可能会在中枢神经系统（CNS）附近肿瘤以及该器官内恶性肿瘤的常规诊断和疗效评估中提供有价值的信息。作为概念验证，我们对一名眼眶结外边缘区淋巴瘤（MZL）患者在诊断时以及治疗后进行疗效评估时进行了[镓]喷替沙福PET成像。与常规进行的[F]FDG PET相比，通过磁共振成像（MRI）确定的淋巴瘤病变在诊断时显示出高示踪剂摄取，治疗后摄取减少。因此，我们提出用[镓]喷替沙福对CXCR4进行成像对于中枢神经系统附近或中枢神经系统内的肿瘤是一种潜在的诊断工具，并建议在临床试验中对此进行研究。
