New imaging tool could transform how doctors treat severe lung disease
Researchers have developed a PET scanner tracer that can visualize inflammation in damaged lungs, potentially enabling doctors to personalize treatment for conditions like pulmonary fibrosis. The breakthrough addresses a critical gap: clinicians currently lack ways to measure inflammation non-invasively, making it difficult to predict which patients will benefit from expensive anti-inflammatory drugs.
Originaltitel: Positron Emission Tomography imaging of tumor necrosis factor in lung injury
**PET-tracer avslöjar lungödem före symptom — öppnar vägen för målinriktad TNF-terapi** Lungödem drivs ofta av inflammatoriska cytokinen TNF, men läkare saknar verktyg för att mäta TNF-aktivitet utan invasiv provtagning. Uppsala universitet presenterar [Ga-68]Z(0185), en ny PET-tracer baserad på Affibody-molekyler, som detekterar TNF-driven inflammation direkt i lungvävnad. Forskare märkte radionuklidet gallium-68 på molekylen med radiokemisk renhet över 95 procent. I råttmodell med bleomycin-inducerad lungskada visade PET-avbildningen dubbel så högt tracer-upptag i inflammerad lung jämfört med frisk vävnad (SUVmean 0,58 mot 0,25, statistiskt signifikant). Makrofaginfiltration bekräftades histologiskt. För regionvården betyder detta potentialen att stratifiera idiopatisk lungfibros-patienter före behandling och övervaka TNF-inhibitors effekt objektivt. Gatekeepern är nu regulatorisk vägledning för klinisk validering — Uppsala universitet leder utvecklingen mot först diagnostisk användning för personaliserad lungbehandling.
<p><strong>Introduction</strong></p><p>Tumor necrosis factor (TNF) is a key pro-inflammatory cytokine involved in various pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), where it contributes to immune cell recruitment, tissue remodeling, and disease progression. Despite the therapeutic potential of TNF-targeting strategies, the lack of non-invasive tools to assess TNF activity in the lungs limits personalized treatment and trial stratification. This study aimed to evaluate the novel Affibody molecule-based positron emission tomography (PET) tracer [Ga-68]Z(0185), targeting TNF, for its ability to detect inflammation in vivo using the bleomycin (BLM)-induced lung injury model in rats.</p><p><strong>Methods</strong></p><p>DOTA-Z(0185) was generated by solid phase peptide synthesis, and a method for labeling by Gallium-68 was developed. The resulting PET tracer [Ga-68]Z(0185) was evaluated for binding to recombinant TNF by a radioimmuno-assay. [Ga-68]Z(0185) was further evaluated by PET imaging and ex vivo biodistribution studies in a bleomycin rat model of lung injury in comparison with healthy rats.</p><p><strong>Results</strong></p><p>DOTA-Z(0185) was consistently radiolabeled with a radiochemical purity of at least 95%. [Ga-68]Z(0185) bound to recombinant human TNF in vitro with a mechanism that could be partially inhibited by etanercept (131.8 +/- 12.0 vs. 74.2 +/- 5.6 fmol, P < 0.05). [Ga-68]Z(0185) uptake was significantly higher in injured pulmonary regions in BLM-treated rats compared to lung tissue in control animals (SUVmean 0.58 +/- 0.22 vs. 0.25 +/- 0.07, P < 0.05) as analyzed by PET/computed tomography (CT) in vivo imaging. These regions corresponded with histologically confirmed areas of inflammation, with dense CD68+ macrophage infiltration.</p><p><strong>Conclusion</strong></p><p>[Ga-68]Z(0185) enables non-invasive detection of localized TNF-driven inflammation in the lung. This approach offers a promising imaging tool for patient stratification, therapy monitoring, and guiding anti-TNF interventions in pulmonary diseases.</p>