Quantification of pulmonary vascular remodelling in pulmonary arterial hypertension patients using positron emission tomography

There is a urgent need for an imaging method for the non-invasive
quantification of pulmonary vascular remodeling in patients with pulmonary
arterial hypertension (PAH). Characteristic features of the vascular pathology
of PAH are vascular obstructions due to the presence of hyperproliferative
endothelial and smooth muscle cells, increased expression of several growth
factor receptors (PDGF-R, EGF-R, FGF-R). Since there is an increasing interest
in the development of drugs directly targeting the pulmonary vascular
remodeling, there is a need of a non-invasive quantification of the pulmonary
vascular remodeling which would not only reflect the underlying disease process
in PAH patients, but would also predict responses to PAH treatment.

To non-invasively quantify pulmonary vascular remodeling in pulmonary arterial
hypertension using [18F]-FLT (determination hyperproliferation).

In this pilot study we will prospectively include 8 idiopathic pulmonary
arterial hypertension patients and measure the uptake patterns of the existing
PET tracers [18F]-FLT in the lung. We will compare the uptake patterns of this
8 patients with existing data sets of non-PH controls.

The scan will be performed on 1 days. Scans will be performed during standard
follow-up of patients. Therefore patients dont have to be admitted to the
hospital for only this study.

Venous cannulas will be placed by highly qualified medical doctors of the
Department of Pulmonary Diseases. Occasionally cannulas may cause a hematoma.
The total amount of blood withdrawn will be 60 ml per patient for the complete
study. The total scan duration will be 70 minutes.The total amount of radiation
burden will be around 6 mSv during the entire study. To compare, every person
living in the Netherlands receives a natural background radiation dose of 2-2,5
mSv per year.According to the *Radiological Protection in Biomedical Research
(ICRP) guidelines* which provides justification for biomedical research with
ionized radiation, the level of risk related to radiation exposure, is minor to
intermediate if the effective dose is below ore equal to 10mSv. No side effects
are suspected of the PET tracer [18F]-FLT.

We are aware that the radiation burden for this study is high, but we think
that this is acceptable for this particular study (high scientific impact). The
results of this study can have great clinical benefit since there is an urgent
need for an imaging method for the non-invasive quantification of pulmonary
vascular remodelling which can theoretically not only reflect the primary
disease process in PAH, but also predict and assess the response to treatment.