SPECT Imaging of Chronic Thromboembolic Pulmonary Hypertension Using a Pulmonary Vascular Endothelium Tracer

Abstract

Objectives: PulmoBind was developed for molecular imaging of pulmonary vascular diseases. It is a high affinity specific ligand of the adrenomedullin receptor that is densely expressed in the pulmonary vascular endothelium. A phase II safety and proof of concept study with PulmoBind was completed in 30 pulmonary hypertension patients, including 7 CTEPH subjects (ClinicalTrials.gov NCT02216279). In this sub-analysis we explored the potential of PulmoBind for the diagnosis of CTEPH. Methods: Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed 35 minutes after injection of 15 mCi 99mTc‑PulmoBind in supine position. The scans were blindly read to describe the presence of segmental perfusion defects suggestive of pulmonary embolism. Previous lung scans performed 2.18 ± 2.39 years before with macro-aggregates of albumin (MAAs) were available in 4 CTEPH subjects and compared to the PulmoBind scans. Results: All subjects completed the study with no serious adverse events or safety concerns. The overall mean labeling efficiency of 99mTc-PulmoBind was 98% ± 2% and mean injected activity was 14.6 ± 1.82 mCi. The 7 CTEPH subjects (61 ± 9.8 years) had a mean pulmonary artery systolic pressure of 62 ± 27 mmHg at cardiac ultrasound. All CTEPH (7/7) were interpreted as having segmental perfusion defects compatible with pulmonary embolism, and for PAH it was 2/23 subjects. There were no perfusion defects in the 15 healthy subjects. Although non-contemporary and performed with different acquisition protocols, perfusions defects detected with PulmoBind were comparable to those visualized with MAAs (figure). Conclusion: This exploratory analysis suggests that the pulmonary vascular endothelium tracer PulmoBind could be of value in the diagnosis of lung perfusion defects caused by CTEPH. Studies with direct comparison to MAAs lung scans and angio-CT are justified.