Prolonged hematopoietic and myeloid cellular response in patients after an acute coronary syndrome measured with 18F-DPA-714 PET/CT

Abstract

An acute coronary syndrome (ACS) is characterized by a multi-level inflammatory response, comprising activation of bone marrow and spleen accompanied by augmented release of leukocytes into the circulation. The duration of this response after an ACS remains unclear. Here, we assessed the effect of an ACS on the multi-level inflammatory response in patients both acutely and after 3 months. We performed 18F-DPA-714 PET/CT acutely and 3 months post-ACS in eight patients and eight matched healthy controls. DPA-714, a PET tracer binding the TSPO receptor and highly expressed in myeloid cells, was used to assess hematopoietic activity. We also characterized circulating monocytes and hematopoietic stem and progenitor cells (HSPCs) by flow cytometry in 20 patients acutely and 3 months post-ACS and in 19 healthy controls. In the acute phase, patients displayed a 1.4-fold and 1.3-fold higher 18F-DPA-714 uptake in, respectively, bone marrow (p = 0.012) and spleen (p = 0.039) compared with healthy controls. This coincided with a 2.4-fold higher number of circulating HSPCs (p = 0.001). Three months post-ACS, 18F-DPA-714 uptake in bone marrow decreased significantly (p = 0.002), but no decrease was observed for 18F-DPA-714 uptake in the spleen (p = 0.67) nor for the number of circulating HSPCs (p = 0.75). 18F-DPA-714 PET/CT reveals an ACS- triggered hematopoietic organ activation as initiator of a prolonged cellular inflammatory response beyond 3 months, characterized by a higher number of circulating leukocytes and their precursors. This multi-level inflammatory response may provide an attractive target for novel treatment options aimed at reducing the high recurrence rate post-ACS.