Pulmonary serotonin transporter availability in patients with COPD and pulmonary hypertension

Background Pulmonary hypertension (PH) is a hemodynamic condition characterized by progressive remodeling of the pulmonary vasculature resulting in right heart failure and death. Serotonin transporter (SERT) is assumed to be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time SERT in vivo availability in the lungs of patients with COPD and PH.

Methods SERT availability was assessed by means of SERT-selective [¹¹C]DASB measured by positron emission tomography/computed tomography (PET/CT) with dynamic acquisition over 30 min in four groups (N = 5 each): pulmonary arterial hypertension (PAH), COPD, COPD+PH, and healthy control (HC). Time activity curves were generated based on a volume of interest within the middle lobe. Pulmonary tissue uptake after 25 to 30 min (SUV_25-30) served as non-model based parameter for group comparison and were corrected for blood activity (tissue-to-blood concentration ratio [TTBR_25-30]) and for lung tissue attenuation based on Hounsfield units (HU). Pulmonary workup included right heart catheterization, pulmonary function test, six minute walking distance (6MWD) test, and serum concentration of N-terminal pro-brain natriuretic peptide, the calculation of the oxygenation ratio (arterial oxygen tension/inspiratory oxygen fraction) and alveolar-arterial gradient. Statistical analysis included analysis of covariance for group comparisons and partial Spearman rank correlation analysis (ρ) to adjust for lung tissue attenuation of the middle lobe, respectively. Statistical significance was accepted at a level of a two-sided P < 0.05.

Results Both COPD and COPD+PH cohorts showed significant lower values of TTBR_25-30 as compared with HC, whereas TTBR_25-30 was significantly higher in COPD+PH and PAH as compared with COPD. HU corrected TTBR_25-30 positively correlated with invasively measured pulmonary vascular resistance (ρ = 0.65, P = 0.04), with FEV1/FVC (ρ = 0.72, P = 0.002) and 6MWD (ρ = 0.79, P = 0.004), but negatively with arterial carbon dioxide tension (ρ = -0.68, P = 0.02) and total airway resistance (ρ = -0.72, P = 0.002).

Conclusions SERT is detectable in the lung vasculature using [¹¹C]DASB-PET/CT. TTBR_25-30 positively correlated with severity of PH and inversely with severity of COPD, indicating an implication of pulmonary SERT in COPD+PH.