[68Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity

被引:69
作者
Rosenkrans, Zachary T. [1 ]
Massey, Christopher F. [1 ]
Bernau, Ksenija [2 ]
Ferreira, Carolina A. [1 ]
Jeffery, Justin J. [3 ]
Schulte, Jefree J. [4 ]
Moore, Melissa [5 ]
Valla, Frank [5 ]
Batterton, Jeanine M. [1 ]
Drake, Christopher R. [5 ]
McMillan, Alan B. [1 ]
Sandbo, Nathan [2 ]
Pirasteh, Ali [1 ,6 ]
Hernandez, Reinier [1 ,3 ,6 ]
机构
[1] Univ Wisconsin, Dept Med Phys, 1111 Highland Ave,Room 7137, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Med, Div Allergy Pulm & Crit Care Med, Sch Med & Publ Hlth, Madison, WI USA
[3] Univ Wisconsin, Univ Wisconsin Carbone Canc Ctr, Madison, WI 53706 USA
[4] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA
[5] SOFIE, Dulles, VA USA
[6] Univ Wisconsin, Dept Radiol, 1111 Highland Ave,Room 2423, Madison, WI 53705 USA
关键词
Fibroblast activation protein; Idiopathic; Pulmonary fibrosis; Positron emission tomography imaging; Ga-68] Ga-FAPI-46; FIBROBLAST ACTIVATION PROTEIN; PATHOGENESIS; EXPRESSION; MORTALITY; MODEL; CANCER; ALPHA; FAP;
D O I
10.1007/s00259-022-05814-9
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis. Methods Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3-5) underwent dynamic 1 h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([Ga-68]Ga-FAPI-46) at 7 days and 14 days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [Ga-68]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis. Results CT only detected differences in the fibrotic response at 14 days post-bleomycin administration. [Ga-68]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7 days and 14 days. Significantly (P = 0.0012) increased [Ga-68]Ga-FAPI-46 lung uptake in the bleomycin groups at 14 days (1.01 +/- 0.12%IA/cc) vs. 7 days (0.33 +/- 0.09%IA/cc) at 60 min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology. Conclusion CT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients.
引用
收藏
页码:3705 / 3716
页数:12
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