Hovhannisyan Narinée, Guillouet Stéphane, Fillesoye Fabien, Dhilly Martine, Patin Delphine, Galateau Françoise, Leporrier Michel, Barré Louisa
CEA, DSV/I2BM, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France ; Université de Caen Basse-Normandie, Esplanade de la Paix, 14032 Caen, France ; CNRS, UMR ISTCT 6301, LDM-TEP group, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074 Caen, Cedex France.
CHU de Caen, Service d'Anatomie Pathologique, Av. de la Côte de Nacre, BP 95182, 14033 Caen, Cedex France.
EJNMMI Res. 2015 Apr 14;5:23. doi: 10.1186/s13550-015-0101-7. eCollection 2015.
[(18)F]Fludarabine is a novel positron emission tomography (PET) radiotracer for imaging lymphoma. The purpose of this preclinical study was to evaluate the robustness of [(18)F]fludarabine during rituximab therapy. In addition, a comparison was made between [(18)F]fludarabine and [(18)F]fluorodeoxyglucose ([(18)F]FDG) with regard to their concordance with histologically derived data.
CB17-SCID mice bearing human follicular DOHH-2 lymphoma were treated once weekly with rituximab (10 mg/kg) or physiological saline over 3 weeks. To obtain the tracer uptake in the metabolically active volume of the tumour (MAVT), a background-level threshold was applied to the volume of interest (VOI) defined on computed tomography (CT) image. The tumour uptake analysis was performed with MAVT-based segmentation for data analysis of sequential [(18)F]fludarabine PET/CT studies and with total tumour-based segmentation for comparison with histologically derived data.
The correlation between the MAVT and [(18)F]fludarabine accumulation (%ID) in those viable tissues was equally significant for both vehicle- or rituximab-treated mice; for these latter, the presence of lymphoid tissues at the end of imaging sessions was confirmed histologically. A stronger correlation was demonstrated between quantitative values extracted from [(18)F]fludarabine-PET and histology (r (2) = 0.91, p < 0.001) when compared to [(18)F]FDG-PET (r (2) = 0.55, p = 0.03).
[(18)F]Fludarabine uptake in the follicular lymphoma model compared favourably with [(18)F]FDG in terms of specificity for PET imaging and also remained robust for persistent viable tissues following rituximab therapy. [(18)F]Fludarabine PET/CT may be a promising approach to evaluate lymphoma, including their surveillance during therapy.
[(18)F]氟达拉滨是一种用于淋巴瘤成像的新型正电子发射断层扫描(PET)放射性示踪剂。这项临床前研究的目的是评估[(18)F]氟达拉滨在利妥昔单抗治疗期间的稳定性。此外,还对[(18)F]氟达拉滨和[(18)F]氟脱氧葡萄糖([(18)F]FDG)与组织学数据的一致性进行了比较。
携带人滤泡性DOHH-2淋巴瘤的CB17-SCID小鼠在3周内每周接受一次利妥昔单抗(10mg/kg)或生理盐水治疗。为了获得肿瘤代谢活跃体积(MAVT)中的示踪剂摄取,对计算机断层扫描(CT)图像上定义的感兴趣体积(VOI)应用背景水平阈值。肿瘤摄取分析采用基于MAVT的分割方法对连续的[(18)F]氟达拉滨PET/CT研究进行数据分析,并采用基于肿瘤总体积的分割方法与组织学数据进行比较。
在接受载体或利妥昔单抗治疗的小鼠中,MAVT与[(18)F]氟达拉滨在这些存活组织中的蓄积(%ID)之间的相关性同样显著;对于后者,成像结束时淋巴组织的存在通过组织学得到证实。与[(18)F]FDG-PET(r(2)=0.55,p=0.03)相比,从[(18)F]氟达拉滨-PET提取的定量值与组织学之间的相关性更强(r(2)=0.91,p<0.001)。
在PET成像特异性方面,滤泡性淋巴瘤模型中[(18)F]氟达拉滨的摄取与[(18)F]FDG相比具有优势,并且在利妥昔单抗治疗后对持续存活组织仍保持稳定性。[(18)F]氟达拉滨PET/CT可能是评估淋巴瘤的一种有前景的方法,包括在治疗期间对其进行监测。