Institute of Neuroscience and Medicine (INM-3, -4, -5), Forschungszentrum Jülich, 52425, Jülich, Germany.
Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Lorraine University, Nancy, France.
Mol Imaging Biol. 2018 Dec;20(6):1035-1043. doi: 10.1007/s11307-018-1197-8.
Cis-4-[F]fluoro-D-proline (D-cis-[F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[F]FPro in human brain tumors after multimodal treatment.
In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR, LBR), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [F]FET PET (n = 10).
D-cis-[F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBR 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBR 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[F]FPro uptake. Distribution of [F]FET and D-cis-[F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different.
The high accumulation of D-cis-[F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[F]FPro for treatment monitoring.
顺式-4-[F]氟-D-脯氨酸（D-顺式-[F]FPro）已被证明可以穿过完整的血脑屏障，并在大鼠脑的继发性神经退行性变和坏死区域积聚，而在实验性脑肿瘤中的摄取则较低。本初步研究探讨了多模态治疗后 D-顺式-[F]FPro 在人脑肿瘤中的摄取行为。
在一项前瞻性研究中，对 27 例经手术、放疗和/或化疗（SRC）治疗后疑似复发性脑肿瘤的患者进行动态正电子发射断层扫描（PET）检查，使用 D-顺式-[F]FPro（22 例高级别胶质瘤、1 例未特指的胶质瘤和 4 例转移瘤）。此外，还包括 2 例未经治疗的病变患者（1 例胶质母细胞瘤，1 例反应性星形细胞瘤）。将数据与使用 O-[2-[F]氟乙基]-L-酪氨酸（[F]FET）进行的 PET 结果进行比较，[F]FET 可检测存活的肿瘤组织。评估示踪剂摄取的时间活性曲线（TAC）的示踪剂分布、平均和最大病变与脑比（LBR、LBR）以及达峰时间（TTP）。最终诊断通过组织学（n=9）、临床随访（n=10）或[F]FET PET（n=10）确定。
D-顺式-[F]FPro 在复发性脑肿瘤（n=11）和仅被归类为治疗相关改变（TRC）的病变（n=16）中均表现出高摄取（LBR 2.2±0.7 和 2.1±0.6，无统计学差异；LBR 3.4±1.2 和 3.2±1.3，无统计学差异）。未经治疗的胶质母细胞瘤和表现出反应性星形胶质增生的病变摄取 D-顺式-[F]FPro 较低。29 例中有 21 例[F]FET 和 D-顺式-[F]FPro 摄取分布不一致，表明摄取机制不同。
预处理脑肿瘤和 TRC 中 D-顺式-[F]FPro 的高积聚支持示踪剂摄取与细胞死亡有关的假说。需要在治疗前后进行进一步的研究，以评估 D-顺式-[F]FPro 用于治疗监测的潜力。
