Lung SERT availability in patients with pulmonary hypertension (PH)

 

Ziel/Aim:

PH is a hemodynamic condition of various causes characterized by progressive remodeling of the pulmonary vasculature resulting in right heart failure and death. The role of the serotonin transporter (SERT) in the pathogenesis of PH in chronic-obstructive pulmonary disease (COPD) is still discussed controversial. The study investigated lung SERT availability of patients with COPD and PH, with COPD, with idiopathic pulmonary arterial hypertension (IPAH) and healthy volunteers (HV) for the first time in vivo.

Methodik/Methods:

SERT availability was assessed using PET-CT (Biograph 16) and SERT-selective [¹¹C]DASB (495 ± 6 MBq, 30-min dynamic acquisition) in four well-matched groups (N = 5 each) of patients with IPAH (age 57 ± 8 years), COPD (57 ± 3 years), COPD+PH (56 ± 10 years), as well as in HV (56 ± 8 years). Time activity curves were generated in a single-volume of interest (VOI) manually defined in coregistered PET-CT data. The tissue- to plasma-concentration ratio between 25 to 30 min (TTPR_{25 – 30}) as approximation of the distribution volume and the standardized uptake value from 25 to 30 min SUV_{25 – 30} was used as nonmodel-based receptor parameter in group comparison. To assess differences in perfusion and delivery (K1), we used SUV during 0 – 3 min p.i. (SUV_{0 – 3}) considering the tissue density based on Hounsfield units (HU) in the same VOI as a covariate.

Ergebnisse/Results:

HU-corrected SUV_{0 – 3} did not differ between the groups. While SUV_{25 – 30} between HC and IPAH were not different (5.4 ± 1.7 and 4.2 ± 1.1, p = 0.23), there were significant lower values in both COPD and COPD+PH compared with HV (1.8 ± 0.1, p = 0.004, and 3.2 ± 0.8, p = 0.03). Accordingly, TTPR_{25 – 30} was significantly lower in COPD/COPD+PH compared with HV while IPAH and HV did not show significant TTPR_{25 – 30} difference. Compared with COPD+PH, patients with COPD had significantly lower SUV_{25 – 30} (p = 0.02) and TTPR_{25 – 30} which differ with borderline significance (p = 0.054).

Schlussfolgerungen/Conclusions:

These data demonstrate that SERT in the lung vasculature is detectable using [¹¹C]DASB. They also indicate that pulmonary SERT availability differs between patients with COPD and COPD+PH. Further studies are necessary to investigate the importance of these preliminary findings.

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