The Persian Gulf Nuclear Medicine Research Center, Department of Molecular Imaging and Radionuclide Therapy, Bushehr Medical University Hospital, Bushehr University of Medical Sciences, Bushehr.
From the Division of Hematology/Oncology, Department of Pediatrics, School of Medicine.
Clin Nucl Med. 2021 Jul 1;46(7):540-548. doi: 10.1097/RLU.0000000000003577.
Recent evidence has demonstrated high expression of somatostatin receptors in neuroblastoma (NB) cells. Because of this, we endeavored to evaluate the diagnostic performance and clinical efficacy of 68Ga-DOTATATE PET/CT and peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE combined with chemotherapy in pediatric NB patients.
In total, 14 pediatric patients with histopathologically confirmed NB underwent 68Ga-DOTATATE PET/CT. Among them, the patients who were refractory or relapsed after therapy with 131I-MIBG and had intensive uptake of 68Ga-DOTATATE were referred for PRRT using 177Lu-DOTATATE. Treatment response based on follow-up imaging was classified into complete response, partial response, stable disease, and progressive disease. After each cycle of PRRT, laboratory tests were performed for evaluation of hematological, renal, and hepatic toxicities. The CTCAE (Common Terminology Criteria for Adverse Events; version 4.03) was used for grading adverse event. Curie score and International Society of Pediatric Oncology Europe Neuroblastoma score were used for semiquantitative analysis of scans of patients who underwent PRRT. In addition, overall survival was calculated as the time interval between the date of the first cycle and the end of follow-up or death.
Overall, 14 refractory NB children including 7 boys and 7 girls with a median age of 5.5 years (ranged from 4 to 9) underwent 68Ga-DOTATATE PET/CT. PET/CT was positive in 10/14 patients (71.4%), and the median number of detected lesions in positive patients was 2 (range, 1-13). Of 14 patients, 5 patients underwent PRRT, including 3 boys and 2 girls. A total of 19 PRRT cycles and 66.4 GBq 177Lu-DOTATATE were given. Among these 5 patients, 2 showed an initial complete response, which relapsed a few months later, 1 showed a partial response, and 2 showed progressive disease. According to the Kaplan-Meier test, the overall survival was estimated at 14.5 months (95% confidence interval, 8.9-20.1). In evaluation of PRRT-related toxicity according to the CTCAE, 4 patients showed grade 1, and 1 showed grade 2 leukopenia. Two patients showed grade 1, and 2 others showed grade 2 anemia. Two patients showed grade 1, and 3 patients showed grade 2 thrombocytopenia. Serum creatinine in 1 patient increased to grade 1.
Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.
最近的证据表明，神经母细胞瘤（NB）细胞中生长抑素受体表达水平较高。因此，我们试图评估 68Ga-DOTATATE PET/CT 的诊断性能和临床疗效，并结合 177Lu-DOTATATE 肽受体放射性核素治疗（PRRT）在儿科 NB 患者中的应用。
共 14 例经组织病理学证实的 NB 患儿接受了 68Ga-DOTATATE PET/CT 检查。其中，经 131I-MIBG 治疗后出现耐药或复发且 68Ga-DOTATATE 摄取强烈的患者，被转诊接受 177Lu-DOTATATE PRRT。根据随访影像学检查将治疗反应分为完全缓解、部分缓解、稳定疾病和进展性疾病。在每个 PRRT 周期后，进行实验室检查以评估血液学、肾脏和肝脏毒性。采用 CTCAE（不良事件常用术语标准；版本 4.03）对不良事件进行分级。使用 Curie 评分和欧洲小儿肿瘤学会神经母细胞瘤评分对接受 PRRT 的患者的扫描进行半定量分析。此外，总生存时间计算为从第一周期开始到随访结束或死亡的时间间隔。
共有 14 例耐药性 NB 患儿（7 名男孩和 7 名女孩），中位年龄为 5.5 岁（4-9 岁），接受了 68Ga-DOTATATE PET/CT 检查。14 例患者中，10 例（71.4%）PET/CT 阳性，阳性患者中检测到的病变中位数为 2 个（范围，1-13）。在 14 例患者中，5 例接受了 PRRT，包括 3 名男孩和 2 名女孩。共进行了 19 个 PRRT 周期，给予了 66.4GBq 177Lu-DOTATATE。在这 5 名患者中，2 名患者最初完全缓解，几个月后复发，1 名患者部分缓解，2 名患者疾病进展。根据 Kaplan-Meier 检验，总生存时间估计为 14.5 个月（95%置信区间，8.9-20.1）。根据 CTCAE 评估 PRRT 相关毒性，4 例患者出现 1 级白细胞减少症，1 例患者出现 2 级贫血症。2 例患者出现 1 级，2 例患者出现 2 级血小板减少症。1 例患者的血清肌酐升高至 1 级。
177Lu-DOTATATE 联合化疗药物可能具有良好的疗效，且毒性较低，这为常规治疗（包括 131I-MIBG 治疗）后复发或耐药的 NB 患者提供了生存机会。在这些患者中，68Ga-DOTATATE PET/CT 成像具有较高的检测效果，表明其作为传统成像方式（如 123I/131I-MIBG）的替代成像工具具有一定潜力。但是，仍需要开展更多精心设计的临床试验。
