Molecular Imaging of Fibroblast Activity After Myocardial Infarction Using a ⁶⁸Ga-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04

In vivo dynamic imaging of ⁶⁸Ga-FAPI-04 uptake. (A) Serial PET/CT images (axial and coronal sections) from 90-min dynamic scan of MI rat at 7 d after coronary ligation. Representative regions of interest (2-dimensional) drawn over infarct border zone and remote myocardium are illustrated as red and black circles, respectively. Regions of interest in infarcts were placed relatively far from surgical wounds. ⁶⁸Ga-FAPI-04 exhibited elevated uptake in scars from operation (asterisk). (B) Corresponding time–activity curves for infarcted and noninfarcted heart tissue (average and SD, n = 3). (C) Infarct-to-noninfarct ratio over time (average and SD, n = 3). H = heart; Li = liver; p.i. = after injection.

In vivo imaging of ⁶⁸Ga-FAPI-04 uptake in longitudinal study. (A) Static PET/CT matched axial slices in same rat subjected to coronary ligation and scanned 1 h after injection of ⁶⁸Ga-FAPI-04 (1, 3, 6, 14, 23, and 30 d after MI) and ¹⁸F-FDG (3 d after MI). Dashed lines separate tracer uptake in myocardium from uptake in surgical wounds. In 6 d after MI image, representative regions of interest (2-dimensional) drawn over infarct border zone and remote myocardium are illustrated as red and black circles, respectively. ⁶⁸Ga-FAPI-04 uptake in regions of interest of infarcts is demonstrated. (B) Corresponding time–activity curves for infarcted and noninfarcted heart tissue (average and SD, n = 3). ⁶⁸Ga-FAPI-04 and ¹⁸F-FDG exhibited elevated uptake in scars from operation (asterisk).

Axial sections of in vivo PET/CT imaging with ¹⁸F-FDG (day 3 after MI) and ⁶⁸Ga-FAPI-04 (day 6 after MI) and corresponding ex vivo PET/MRI with ⁶⁸Ga-FAPI-04 (day 7 after MI). ¹⁸F-FDG image was used to identify areas of infarcted myocardium (arrow), where increased uptake of ⁶⁸Ga-FAPI-04 was apparent (arrowhead). ⁶⁸Ga-FAPI-04 exhibited elevated uptake in postsurgical scar (asterisk). Dashed line separates ⁶⁸Ga-FAPI-04 uptake in myocardium from surgical wound. High-resolution MR and PET/MR data confirmed infarcted area, where ⁶⁸Ga-FAPI-04 uptake was increased.

Binding specificity test. (A) PET/CT axial views, autoradiographs, and corresponding H&E stainings of 10-μm cross-sections prepared from MI nonblocked, blocked, and sham-operated rats. Autoradiographs and H&E stainings from nonblocked hearts show increased ⁶⁸Ga-FAPI-04 uptake in infarcted area at 7 d after MI, whereas uptake is negligible after sham operation or injection of nonlabeled FAPI-04 (blocked). Infarcted areas in H&E stainings are identified with arrows. (B) PET image–derived infarct-to-noninfarct uptake ratio (derived from 6 nonblocked and 3 blocked rat hearts subjected to coronary ligation). (C) Autoradiography image–derived infarct-to-noninfarct uptake ratio (derived from 3 nonblocked and 3 blocked MI hearts). QL = quantum level.

Ex vivo evaluation of ⁶⁸Ga-FAPI-04 uptake in infarct at 7 d after MI. Representative autoradiograph and corresponding H&E staining from rat heart show elevated and heterogeneous uptake of ⁶⁸Ga-FAPI-04 in infarct border compared with infarct center.