论文标题
部分体积校正改善了Theranotic 124i/131i-CLR1404头颈癌的异种移植模型中的肿瘤剂量测定法
Partial volume correction improves theranostic 124I/131I-CLR1404 tumor dosimetry in xenograft models of head and neck cancer
论文作者
论文摘要
放射性药物和外束放射疗法的组合提供了减少局部毒性的潜力，而局部毒性在常规治疗范式中仍然限制了剂量的头部和颈部癌（HNC）。在这项研究中，我们研究了各种HNC异种移植小鼠模型中131I-CLR1404（CLR 131）的肿瘤靶向能力，以及基于124i-CLR1404（CLR 124）PET/CT/CT Imaging的局部体积校正对疗法剂量测定法的影响。方法：使用MicroPET/CT使用MicroPET/CT，在静脉内给予HNC（6鼠细胞系和6种人类患者衍生）的小鼠（6鼠细胞系和6种人类患者衍生）CLR 124的6.5-9.1 MBQ CLR 124。评估了CLR 124的体内肿瘤摄取，并使用新型的临床前幻影应用了124i的部分体积校正（PVC）。使用基于CLR 124成像的CLR 131的受试者特异性治疗剂量测定估计，进行了离散的辐射剂量升级研究，以评估相对于单个XRT的单个部分，以评估对CLR 131的肿瘤生长响应。结果：PET成像表明在所有HNC异种移植模型中，CLR 124的肿瘤选择性摄入量保持一致。在SCC-22B和UW-13中观察到4.4 +/- 0.8％和4.2 +/- 0.4％的峰值吸收。 PVC的应用将摄取量度提高了47-188％，体内和体内摄取测量值的绝对差异从3.3至1.0％IA/g。在所有HNC模型上平均的肿瘤剂量法为0.85 +/- 0.27 Gy/MBQ（使用PVC 1.58 +/- 0.46 Gy/MBQ）。治疗性CLR 131研究表明，CLR 131辐射剂量与肿瘤生长延迟之间存在可变但线性关系（P <0.05）。结论：CLR 131在临床前HNC肿瘤模型中表现出肿瘤能力，而CLR 124/131的Theranostic配对提出了一种有希望的新方法，用于个性化CLR 131。
Combination radiopharmaceutical and external beam radiotherapy offers the potential to diminish locoregional toxicity that remains dose-limiting in the conventional treatment paradigm for recurrent head and neck cancer (HNC). In this study, we investigated the tumor targeting capacity of 131I-CLR1404 (CLR 131) in various HNC xenograft mouse models and the impact of partial volume correction on theranostic dosimetry based on 124I-CLR1404 (CLR 124) PET/CT imaging. Methods: Mice bearing flank tumor xenograft models of HNC (6 murine cell line- and 6 human patient-derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of six days using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and partial volume corrections (PVC) for 124I were applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for CLR 131 based on CLR 124 imaging, a discrete radiation dose escalation study was performed to evaluate tumor growth response to CLR 131 relative to a single fraction of XRT. Results: PET imaging demonstrated consistent tumor selective uptake and retention of CLR 124 across all HNC xenograft models. Peak uptake of 4.4 +/- 0.8% and 4.2 +/- 0.4% was observed in SCC-22B and UW-13, respectively. PVC application increased uptake measures by 47-188% and reduced absolute differences between in vivo and ex vivo uptake measurements from 3.3 to 1.0 %IA/g. Tumor dosimetry averaged over all HNC models was 0.85 +/- 0.27 Gy/MBq (1.58 +/- 0.46 Gy/MBq with PVC). Therapeutic CLR 131 studies demonstrated a variable, but linear relationship between CLR 131 radiation dose and tumor growth delay (p < 0.05). Conclusion: CLR 131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing of CLR 124/131 presents a promising new treatment approach for personalizing administration of CLR 131.
