Magnetic nanoradiotracers for targeted neutrophil detection in pulmonary arterial hypertension

Inflammation is thought to play a pivotal role in the progression of pulmonary arterial hypertension (PAH). This study aims to provide more understanding of the inflammatory proces by investigating the role of neutrophil infiltration in PAH. The neutrophil infiltration was quantified in vivo in rat models with different inflammation profiles (and degree of neutrophil infiltration) using targeted PET imaging.

For this purpose, ligand-functionalized iron oxide ultrasmall nanoparticles (68Ga-IONP-cFLFLF) were evaluated as multimodal nanotracers for both magnetic resonance imaging (MRI) and PET to detect increased neutrophil infiltration and compare to the gold standard for assessing inflammation, 18F-FDG.

PET and micro-CT imaging were performed in two PAH rat models using the β-CUBE (PET) and X-CUBE (CT). Monocrotaline (MCT) and double-hit Sugen-chronic hypoxia (SuHx) PAH rat models were investigated and compared to a healthy group.

For the PET scan, rats were intravenously injected with either 18F-FDG (3.7-6.7 MBq) or 68Ga-IONP-cFLFLF (2.4-5.6 MBq) and imaged 30 minutes post-administration by static 10 min whole-body scans. The image aquisition was performed using a 511 keV ± 30% energetic window.

The CT scans were performed right after to provide anatomic context and attenuation correction for the detected radioactive signal. The individual organs were outlined based on CT to define volumes of interest. This was used as a reference to quantify the mean standard uptake values (SUVmean) on the PET images (activity values normalized to the initial radioactivity).

68Ga-IONP-cFLFLF as a magnetic nanoradiotracer showed promise for the targeted detection of neutrophils associated with inflammation in PAH animal models. These findings suggest that this nanoprobe can be used to investigate cell-specific inflammatory processes in PAH and the role of neutrophils in chronic inflammation. The similar 18F-FDG uptake in healthy and PAH animals suggests it doesn’t reflect changes in inflammatory cells or vascular remodeling.

The PET imaging using this novel nanoradiotracer elucidated differences between the neutrophil infiltration in MCT and SuHx rat models. The authors observed a higher SUVmean in the MCT rat lung tissue in contrast to the SuHx rats, which showed a similar signal as those measured in the control group.

This study demonstrates for the first time the possibility to image neutrophil inflitration in PAH models non-invasively, highlighting the importance of imaging in the understanding of such a heterogeneous diseases.

The use of the multimodal nanoprobe for MRI/PET imaging has the potential to facilitate the diagnosis and monitoring of diseases, as well as the development of novel therapies.

Figure from Fadón-Padilla et al. Journal of Nanobiotechnology (2024) 22:709