Background Fibroblasts are the key cells among the noncardiomyocytes who play a vital role in cardiac fibrosis, remodelling and failure. The present study evaluates whether fibroblast activation protein (FAP) targeting positron emission tomography (PET) tracer [⁶⁸Ga]-DOTA-FAP5 detects fibroblast activation in a mouse model of pressure overload.

Materials and methods C57BL/6NRj mice underwent transverse aortic constriction (TAC) surgery (n=18) or sham operation (n=11). Mice were studied either on Day 7 or Day 21 after the surgery. The mice underwent an echocardiography to confirm successful TAC and to evaluate LV function at the time of surgery and at follow-up. The PET imaging was performed with [¹⁸F]FDG to loacalize myocardium followed by [⁶⁸Ga]-DOTA-FAP5 PET on consecutive days. After the [⁶⁸Ga]-DOTA-FAP5 PET the mice were euthanized. Their organs underwent ex vivo radioactivity measurements, whereas the heart was processed to perform Masson’s trichome staining and autoradiography on left ventricle (LV) tissue sections to detect myocardial fibrosis and measure the uptake of [⁶⁸Ga]-DOTA-FAP5, respectively.

Results Myocardial fibrosis was increased after TAC surgery as compared to sham operation. Autoradiography showed increased uptake of [⁶⁸Ga]-DOTA-FAP5 in fibrotic myocardial regions both on Day7 and Day 21 after TAC surgery as compared to sham-operated mice or the non-fibrotic regions of TAC-operated mice. Furthermore, uptake of [⁶⁸Ga]-DOTA-FAP5 was increased throughout the myocardium on Day 21 as compared with those followed up until Day 7 after the TAC operation.

Conclusion Our results indicate that [⁶⁸Ga]-DOTA-FAP5 is a potential PET radiotracer for the detection of fibroblast activation induced by pressure overload.

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