Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls

Abstract

Increased expression of fibroblast activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Methods Forty-one patients who underwent gallium-68conjugated quinoline-based FAP inhibitor ( 68 Ga-FAPI-04) PET/CT for non-cardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of 68 Ga-FAPI-04 in large arterial walls (SUVmax and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Results Focal arterial uptake of 68 Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (Hounsfield Units, HU) (r = -0.27, P < 0.01). Mean TBR in higher-risk patients was greater than lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, P < 0.01).Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Conclusion 68 Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.

Interobserver Agreement Rates on Fibroblast Activation Protein Inhibitor–Directed Molecular Imaging and Therapy

“… 28 Similar results of a large variety of uptake in oncology patients scanned with FAPI-PET have also been reported for the vasculature. 29 As such, given the lower ICC for the blood pool along with previous reports showing a potential interaction in cardio-oncology settings, unaffected liver parenchyma may be better suited for TBR calculations.…”

Radiotracers to Address Unmet Clinical Needs in Cardiovascular Imaging, Part 2: Inflammation, Fibrosis, Thrombosis, Calcification, and Amyloidosis Imaging

“…Another study demonstrated that left ventricular 68 Ga-FAPI uptake correlated with the presence of cardiovascular risk factors such as overweight status (odds ratio, 2.6; P 5 0.023), type 2 diabetes (odds ratio, 2.9; P 5 0.041), and histories of platinum-based chemotherapy (odds ratio, 3.0; P 5 0.034) and chest radiation (odds ratio, 3.5; P 5 0.024) (68). Finally, a retrospective analysis of 68 Ga-FAPI PET/CT images obtained for noncardiovascular indications showed that focal arterial uptake of the tracer correlated negatively with calcification (r 5 20.27, P , 0.01) (69). Several ongoing clinical trials seek to establish the role of FAPI imaging to detect post-MI cardiac fibrosis (NCT04803864, NCT04723953).…”

PET‐MRI of Coronary Artery Disease

“…Immunohistochemical labeling of carotid plaques also found prominent FAPI expression in thin fibrous caps compared to moderate expression in thick caps. 54 As yet, no studies have assessed coronary 68 Ga-FAPI uptake although there is potential for this radiotracer to assess atherosclerotic fibroblast activity in other vascular territories.…”

“…Elevated uptake occurred in non‐calcified arterial segments when compared to advanced chronic lesions and increased arterial uptake in patients with more cardiovascular risk factors. Immunohistochemical labeling of carotid plaques also found prominent FAPI expression in thin fibrous caps compared to moderate expression in thick caps 54 . As yet, no studies have assessed coronary 68 Ga‐FAPI uptake although there is potential for this radiotracer to assess atherosclerotic fibroblast activity in other vascular territories.…”