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A characterization of ABL-101 as a potential tracer for clinical fluorine-19 MRI.
NMR in Biomedicine ( IF 2.9 ) Pub Date : 2019-11-13 , DOI: 10.1002/nbm.4212
Emeline Darçot 1 , Roberto Colotti 1 , David Brennan 2, 3 , Graeme A Deuchar 3 , Celestine Santosh 2, 3 , Ruud B van Heeswijk 1, 4
Affiliation  

The two main challenges that prevent the translation of fluorine-19 (19 F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal-to-noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL-101, an emulsion of perfluoro(t-butylcyclohexane), is a third-generation PFC that is already used in clinical trials, but has not yet been used for 19 F MRI. The objective of this study was therefore to assess the performance of ABL-101 as a 19 F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF3 groups of ABL-101 generated a large well-separated singlet with T2 /T1 ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL-101 in a 0.25 mm3 voxel at 3 T, 37°C and with a 3-minute acquisition time was 7.21mM. After intravenous injection, the clearance half-lives of the ABL-101 19 F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL-101 has 19 F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half-lives similar to PFCs that have previously been used in large doses in non-MRI clinical trials. Overall, ABL-101 is thus a very promising candidate tracer for future clinical trials that use 19 F MRI for cell tracking or the monitoring of inflammation.

中文翻译:

作为临床氟19 MRI潜在示踪剂的ABL-101的表征。

阻止氟19(19 F)MRI用于炎症监测或细胞追踪转化为临床实践的两个主要挑战是(i)注入的全氟化碳(PFC)产生的信噪比相对较低,因此有必要扫描时间长,并且(ii)还需要监管部门批准,并且还需要适用于MRI的PFC的高生物相容性。ABL-101是全氟叔丁基环己烷的乳液,是第三代PFC,已在临床试验中使用,但尚未用于19 F MRI。因此,本研究的目的是评估ABL-101作为19 F MRI示踪剂的性能。在3、9.4和14.1 T的磁场强度下,ABL-101的CF3基团产生了分离良好的大单峰,T2 / T1比分别> 0.27,> 0.14和> 0.05。随着磁场强度的增加,所有弛豫时间都减少了。ABL-101在0.25 mm3体素中在3 T,37°C且采集时间为3分钟时的检出限为7.21mM。静脉注射后,ABL-101 19 F MR信号在小鼠(n = 3)脾脏和肝脏中的清除半衰期分别为6.85±0.45和3.20±0.35天。这些结果表明,ABL-101具有19 F MR特性,与专门为MRI开发的PFC相似,而其清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。ABL-101在0.25 mm3体素中在3 T,37°C和3分钟的采集时间下的检出限为7.21mM。静脉注射后,小鼠(n = 3)脾脏和肝脏中ABL-101 19 F MR信号的清除半衰期分别为6.85±0.45和3.20±0.35天。这些结果表明,ABL-101具有19 F MR特性,与专门为MRI开发的PFC相似,而其清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。ABL-101在0.25 mm3体素中在3 T,37°C且采集时间为3分钟时的检出限为7.21mM。静脉注射后,ABL-101 19 F MR信号在小鼠(n = 3)脾脏和肝脏中的清除半衰期分别为6.85±0.45和3.20±0.35天。这些结果表明,ABL-101具有19 F MR特性,与专门为MRI开发的PFC相似,而其清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。在小鼠(n = 3)的脾脏和肝脏中,ABL-101 19 F MR信号的清除半衰期分别为6.85±0.45和3.20±0.35天。这些结果表明,ABL-101具有19 F MR特性,与专门为MRI开发的PFC相似,而其清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。在小鼠(n = 3)的脾脏和肝脏中,ABL-101 19 F MR信号的清除半衰期分别为6.85±0.45和3.20±0.35天。这些结果表明,ABL-101具有19 F MR特性,与专门为MRI开发的PFC相似,而其清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。它的清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。它的清除半衰期类似于先前在非MRI临床试验中大剂量使用的PFC。总体而言,ABL-101因此是使用19 F MRI进行细胞跟踪或炎症监测的未来临床试验中非常有希望的候选示踪剂。
更新日期:2019-12-20
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