Agool Ali, Slart Riemer H J A, Thorp Kristin K, Glaudemans Andor W J M, Cobben David C P, Been Lukas B, Burlage Fred R, Elsinga Philip H, Dierckx Rudi A J O, Vellenga Edo, Holter Jennifer L
Department of aNuclear Medicine, University of Groningen, University Medical Center Groningen, Groningen, Ther Netherlands.
Nucl Med Commun. 2011 Jan;32(1):17-22. doi: 10.1097/mnm.0b013e328340798c.
Radiotherapy (RT) and chemotherapy are important treatment modalities for a variety of malignant tumor types. During therapy for malignant diseases, often the limitation for further therapy is determined by the capability of the bone marrow to withstand radiochemotherapeutic effects. Evaluation of hematologic toxicity is commonly performed with peripheral blood counts, and occasionally, sampling of marrow through a bone marrow biopsy. Neither method provides a comprehensive assessment, as bone marrow biopsy is invasive, and both are subject to sampling variability. Fluorine-18-3'-fluoro-3'-deoxy-L-thymidine-PET (18F-FLT-PET) is a noninvasive method and related to the rate of DNA synthesis and visualizes the high cycling activity of hematopoietic cells in the bone marrow compartment. To prove the clinical consistency of marrow function and imaging, we investigated populations of patients typically seen in clinical practice, after radiation and chemotherapy. In this feasibility study, patients were evaluated (i) to prove the ability of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT-PET and (ii) to examine the effect of RT and chemotherapy on bone marrow activity and the correlation with clinical findings.
Bone marrow activity in the cervical region of 10 patients with laryngeal carcinoma who received a mean total dose of 68 Gy (range 30-41 fractions) was evaluated with 18F-FLT-PET, before and 1 month after RT. Whole body FLT images were assessed in nine patients with nonseminomatous testicular germ cell tumor, before and 6 months after the last chemotherapy, consisting of four courses of bleomycin, cisplatin, and etoposide. The maximum standardized uptake value (SUVmax) was used to quantify FLT uptake in bone marrow at the standard bone marrow regions.
A significant decrease in 18F-FLT-PET uptake was observed in all the studied laryngeal carcinoma patients in the cervical region after RT of the adjacent bone marrow compartment. Tumor stage and additional field-of-view of RT were inversely related to the 18F-FLT uptake in bone marrow. The mean 18F-FLT SUVmax before RT was 3.0+/-1.34 and after RT was 1.94+/-0.60 (P=0.013). The mean 18F-FLT SUVmax of the spine (Th5-Th12) regions outside the field-of-view of RT were stable and reproducible and not significantly different (5.56+/-1.56 vs. 5.16+/-1.35, P=0.16). Chemotherapy did not result in a significant difference of whole body SUVmax value, with a mean SUVmax of 4.99+/-1.15 prechemotherapy, and a mean SUVmax of 5.28+/-1.0 postchemotherapy (P=0.21). Laboratory analysis of the hematologic parameters confirmed repopulation of the bone marrow.
18F-FLT uptake in the bone marrow decreases after RT, but not after chemotherapy. We conclude that 18F-FLT-PET is a potential noninvasive tool that can be used in the assessment of quantification of cellular division in the hematopoietic organ.
放射治疗（RT）和化疗是多种恶性肿瘤类型的重要治疗方式。在恶性疾病治疗期间，通常进一步治疗的限制取决于骨髓承受放化疗作用的能力。血液学毒性评估通常通过外周血细胞计数进行，偶尔也会通过骨髓活检采集骨髓样本。这两种方法都不能提供全面的评估，因为骨髓活检具有侵入性，且两者都存在采样变异性。氟 - 18 - 3'-氟 - 3'-脱氧 - L - 胸腺嘧啶核苷 - PET（18F - FLT - PET）是一种非侵入性方法，与DNA合成速率相关，可显示骨髓腔中造血细胞的高增殖活性。为了证明骨髓功能与成像的临床一致性，我们对放疗和化疗后临床实践中常见的患者群体进行了研究。在这项可行性研究中，对患者进行评估：（i）以证明18F - FLT - PET可视化和量化骨髓腔活性的能力；（ii）检查放疗和化疗对骨髓活性的影响以及与临床发现的相关性。
对10例喉癌患者进行评估，这些患者接受的平均总剂量为68 Gy（范围为30 - 41分次），在放疗前和放疗后1个月，用18F - FLT - PET评估颈部区域的骨髓活性。对9例非精原性睾丸生殖细胞肿瘤患者在最后一次化疗前和化疗后6个月进行全身FLT图像评估，化疗方案为四个疗程的博来霉素、顺铂和依托泊苷。使用最大标准化摄取值（SUVmax）对标准骨髓区域的骨髓中FLT摄取进行量化。
在对相邻骨髓腔进行放疗后，所有研究的喉癌患者颈部区域的18F - FLT - PET摄取均显著降低。肿瘤分期和放疗的额外视野与骨髓中18F - FLT摄取呈负相关。放疗前18F - FLT的平均SUVmax为3.0±1.34，放疗后为1.94±0.60（P = 0.013）。放疗视野外脊柱（Th5 - Th12）区域的18F - FLT平均SUVmax稳定且可重复，差异无统计学意义（5.56±1.56 vs. 5.16±1.35，P = 0.16）。化疗未导致全身SUVmax值有显著差异，化疗前平均SUVmax为4.99±1.15，化疗后平均SUVmax为5.28±1.0（P = 0.21）。血液学参数的实验室分析证实了骨髓的再增殖。
放疗后骨髓中18F - FLT摄取降低，但化疗后未降低。我们得出结论，18F - FLT - PET是一种潜在的非侵入性工具，可用于评估造血器官中细胞分裂的量化。
