Manoharan Prakash, Lamarca Angela, Navalkissoor Shaunak, Calero Jose, Chan Pei San, Julyan Peter, Sierra Maribel, Caplin Martyn, Valle Juan
The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, UK
The Christie NHS Foundation Trust, ENETS Centre of Excellence, Manchester, UK.
ESMO Open. 2020 Mar;5(2). doi: 10.1136/esmoopen-2019-000650.
Ga-DOTA0-Tyr3-octreotide (Ga-DOTATOC) positron emission tomography-CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT-CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of Ga-DOTATOC using a new 'ready-to-use' Ga-DOTATOC formulation for injection has been developed (Ga-DOTATOC (SomaKIT TOC)).
This study aimed to assess the safety and tolerability of Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service.
A first-in-human phase I/II multicentre, open-label study of a single dose of Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100-200 MBq) in patients with biopsy-proven grade 1-2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months.
Twenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3-4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of Ga-DOTATOC (SomaKIT TOC) were synthesised with the 'kit' over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected.
The new ready-to-use preparation of Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world's first (EMA) licensed Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice.
与已获许可的示踪剂奥曲肽扫描单光子发射计算机断层扫描-计算机断层扫描（OctreoScan SPECT-CT）相比，镓-多柔比星0-酪胺3-奥曲肽（Ga-DOTATOC）正电子发射断层扫描-计算机断层扫描（PET-CT）在胃肠胰神经内分泌肿瘤（GEP-NETs）患者中具有更优的诊断性能。一种使用新型即用型Ga-DOTATOC注射制剂的新制备方法已被开发出来（Ga-DOTATOC（SomaKIT TOC））。
本研究旨在评估Ga-DOTATOC（SomaKIT TOC）的安全性和耐受性，并评估在神经内分泌肿瘤临床影像服务中应用它的可行性和稳健性。
一项针对经活检证实为1-2级GEP-NETs患者的单剂量2 MBq/kg±10%（范围100-200 MBq）Ga-DOTATOC（SomaKIT TOC）的首次人体I/II期多中心、开放标签研究。注射后进行PET-CT检查。对患者进行28天的随访。接下来，我们在一项为期11个月的临床服务评估中应用了这种新的合成方法。
招募了20名同意参与的患者；14名男性，6名女性；平均（标准差）年龄58岁（12）；神经内分泌肿瘤1级（70%），2级（30%）；75%为IV期疾病。12名患者在研究期间经历了至少一次不良事件（AE），无3-4级毒性反应。只有4例不良事件被分类为可能（头痛（n = 1；4%），恶心（1；4%））或很可能（味觉障碍（1；4%），感觉异常（1；4%））与研究制剂有关。在11个月的时间里，使用该“试剂盒”合成了113瓶Ga-DOTATOC（SomaKIT TOC）用于临床应用。只有2/113瓶（1.77%）被拒收。
新型即用型注射用Ga-DOTATOC（SomaKIT TOC）制剂安全且耐受性良好。这导致了世界上首个（欧洲药品管理局）获许可的用于神经内分泌肿瘤患者PET成像的Ga-DOTATOC（SomaKIT TOC）放射性药物。这种制剂可以稳健地应用于常规临床实践。
