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Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study).
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : 2019-12-09 , DOI: 10.1007/s00259-019-04586-z
Pauline T Lukey 1, 2 , Christopher Coello 3 , Roger Gunn 3 , Christine Parker 1 , Frederick J Wilson 1 , Azeem Saleem 3 , Nadia Garman 1 , Maria Costa 1 , Stuart Kendrick 1 , Mayca Onega 3 , Arthur R Kang'ombe 1 , Allan Listanco 3 , James Davies 3 , Joaquim Ramada-Magalhaes 3 , Sara Moz 3 , William A Fahy 1 , Toby M Maher 4, 5 , Gisli Jenkins 6 , Jan Passchier 3 , Richard P Marshall 1
Affiliation  

Abstract

Purpose

The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ). This study sought to quantify expression of αvβ6 in the lungs of healthy humans and subjects with pulmonary fibrosis using the αvβ6-selective [18F]FB-A20FMDV2 PET ligand.

Methods

[18F]FB-A20FMDV2 PET/CT scans were performed in healthy subjects and those with fibrotic lung disease. Standard uptake values (SUV) and volume of distribution (VT) were used to quantify αvβ6 expression. In subjects with fibrotic lung disease, qualitative assessment of the relationship between αvβ6 expression and the distribution of fibrosis on high resolution computed tomography was conducted.

Results

A total of 15 participants (6 healthy, 7 with idiopathic pulmonary fibrosis (IPF) and 2 with connective tissue disease (CTD) associated PF) were enrolled. VT and SUV of [18F]FB-A20FMDV2 were increased in the lungs of subjects with pulmonary fibrosis (PF) compared with healthy subjects. Geometric mean VT (95% CI) was 0.88 (0.60, 1.29) mL/cm3 for healthy subjects, and 1.40 (1.22, 1.61) mL/cm3 for subjects with IPF; and SUV was 0.54 (0.36, 0.81) g/mL for healthy subjects and 1.03 (0.86, 1.22) g/mL for subjects with IPF. The IPF/healthy VT ratio (geometric mean, (95% CI of ratio)) was 1.59 (1.09, 2.32) (probability ratio > 1 = 0.988)) and the SUV ratio was 1.91 (1.27, 2.87) (probability ratio > 1 = 0.996). Increased uptake of [18F]FB-A20FMDV2 in PF was predominantly confined to fibrotic areas. [18F]FB-A20FMDV2 measurements were reproducible at an interval of 2 weeks. [18F]FB-A20FMDV2 was safe and well tolerated.

Conclusions

Lung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects.



中文翻译:

[18F] FB-A20FMDV2正电子发射断层显像在健康和纤维化人肺中对整联蛋白αvβ6的临床定量(PETAL研究)。

摘要

目的

RGD整合素αvβ6通过激活转化生长因子β(TGFβ)在肺纤维化的发病机理中发挥作用。这项研究旨在使用αvβ6选择性[ 18 F] FB-A20FMDV2 PET配体来量化健康人和患有肺纤维化的受试者的肺中αvβ6的表达。

方法

[ 18 F] FB-A20FMDV2 PET / CT扫描在健康受试者和患有肺纤维化疾病的受试者中进行。使用标准摄取值(SUV)和分布体积(V T)量化αvβ6表达。在患有纤维化肺病的受试者中,进行了高分辨率计算机断层扫描对αvβ6表达与纤维化分布之间关系的定性评估。

结果

共有15名参与者(6名健康者,7名特发性肺纤维化(IPF)和2名结缔组织疾病(CTD)相关的PF)参加了研究。与健康受试者相比,[ 18 F] FB-A20FMDV2的V T和SUV在肺纤维化(PF)受试者的肺中升高。几何平均值V Ť(95%CI)为0.88(0.60,1.29)毫升/厘米3为健康受试者,和1.40(1.22,1.61)毫升/厘米3为患有IPF的受试者; 健康受试者的SUV为0.54(0.36,0.81)g / mL,IPF患者的SUV为SUV 1.03(0.86,1.22)g / mL。IPF /健康V T比率(几何平均值,(比率的95%CI))为1.59(1.09,2.32)(概率比率> 1 = 0.988)),SUV比率为1.91(1.27,2.87)(概率比率> 1 = 0.996)。PF中[ 18 F] FB-A20FMDV2的吸收增加主要限于纤维化区域。[ 18 F] FB-A20FMDV2测量值可在2周的间隔内重复进行。[ 18 F] FB-A20FMDV2安全且耐受良好。

结论

与健康受试者相比,PF受试者的[ 18 F] FB-A20FMDV2的肺摄取(整合素αvβ6的表达量度)显着增加。

更新日期:2020-03-19
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