By Jun-Bean Park

Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

Pulmonary artery hypertension (PAH) is a complex and debilitating group of diseases characterized by hyperproliferative remodeling of pulmonary vessels that leads to an increase in pulmonary vascular resistance, excessive afterload on the right ventricle (RV), and, ultimately, the risk of RV failure and death. An important clinical feature of PAH is that its symptoms and signs are nonspecific, which hampers early diagnosis and timely treatment. Unfortunately, current diagnostic tools, such as right heart catheterization and echocardiography, cannot reliably identify patients with early-stage PAH, either because they are too invasive for common use or because they are not accurate enough. Despite the fact that early detection of PAH progression leads to better outcomes, it has been reported that current noninvasive diagnostic techniques are not suitable for monitoring the response to PAH treatment, leaving a huge unmet clinical need. These difficulties also preclude the appropriate initiation and adjustment of PAH therapy, and it is one of the main reasons for the poor prognosis of patients with PAH.

Among the several pathophysiological mechanisms of PAH, there has been intense attention on the role of altered immune process and failure to resolve inflammation in patients with PAH. Among various immune effector cells in PAH, there are multiple lines of evidence that macrophages may play an important role in the development and progression of PAH. Specifically, several experimental and clinical studies consistently show that macrophage infiltration is prominent in animal models of PAH and in patients with PAH. Early recruitment and activation of mannose receptor (MR)-positive macrophages have been found to be essential for the development of PAH animal models and to be increased in the lungs of patients with idiopathic PAH. Furthermore, previous research showed that depletion or inactivation of macrophages could prevent or reverse PAH. Collectively, these observations suggest that molecular imaging of MR-positive macrophages in the lungs can be used for the diagnosis and treatment monitoring of PAH by imaging the inflammatory status of the lungs.

I and my colleagues have recently developed and introduced positron emission tomography (PET) scan with 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), a tracer targeting the MR, for diagnosis and monitoring of PAH. We revealed that the recruitment of macrophages into the lung vasculature could be harnessed to accurately evaluate PAH using 68Ga-NOTA-MSA PET scan in animal PAH models and explored its translational potential in patients with PAH. I believe that imaging of MR-positive macrophages may be promising for diagnosing and monitoring PAH. Now we are trying to find out more specific PET tracers for imaging inflammation in PAH.

Novel molecular imaging in pulmonary artery hypertension