Jouberton Elodie, Schmitt Sébastien, Maisonial-Besset Aurélie, Chautard Emmanuel, Penault-Llorca Frédérique, Cachin Florent
Service de Médecine Nucléaire, Centre Jean PERRIN, Clermont-Ferrand, France.
Imagerie Moléculaire et Stratégies Théranostiques, UMR1240, Université Clermont Auvergne, INSERM, Clermont-Ferrand, France.
Front Oncol. 2021 Dec 20;11:789769. doi: 10.3389/fonc.2021.789769. eCollection 2021.
One of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies evaluating PET imaging with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The [F]FDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter , several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of [F]ML-10 (2-(5-[F]fluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with [F]ML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis). [F]ML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response.
肿瘤学当前面临的挑战之一是开发成像工具，以便早期检测对传统化疗的反应，并在必要时调整治疗策略。几项评估以2-脱氧-2-[F]氟-D-葡萄糖（[F]FDG）进行PET成像作为治疗反应预测工具的研究强调了其特异性和敏感性不足。[F]FDG摄取仅反映肿瘤代谢活性，而非治疗诱导的细胞死亡，而细胞死亡似乎与治疗评估相关。因此，为了评估该参数，近年来已开发了几种细胞死亡放射性示踪剂。然而，其中很少有进入临床试验阶段。本系统评价聚焦于[F]ML-10（2-(5-[F]氟戊基)-2-甲基丙二酸）作为凋亡放射性示踪剂的应用，尤其是作为衡量肿瘤对治疗反应的指标。对使用[F]ML-10进行的临床前和临床研究进行了全面的文献综述。讨论了这种放射性示踪剂的能力和应用及其临床相关性和局限性。大多数研究强调该放射性示踪剂具有良好的靶向凋亡细胞的能力。然而，即使使用更先进的图像分析（基于体素的分析），治疗期间凋亡的增加与放射性示踪剂在肿瘤中的摄取也不相关。[F]ML-10 PET成像未达到目前对早期检测传统化疗治疗反应的临床期望。本综述指出了在临床试验中应用各种凋亡成像策略的挑战、目前可用的图像分析方法以及评估这种治疗反应的分子成像的未来发展方向。
