A novel SPECT-CT imaging platform for quantifying in vivo lung cytokine signals in COPD

Disease-modifying treatments such as monoclonal antibodies can be highly effective in chronic inflammatory diseases such as COPD, but often fail in clinical trials due to heterogeneity of inflammation and imperfect tools to stratify patients to select optimal therapeutic approaches. Molecular imaging provides the potential to transform precision medicine in this field.

We developed and tested a novel molecular imaging platform using therapeutic monoclonal antibodies labelled with SPECT-CT detectable markers to quantify in vivo tumour necrosis factor (TNF) involved in chronic lung inflammation in humans. We undertook a proof-of-concept clinical study involving participants with COPD and healthy controls. Participants underwent SPECT-CT imaging at 6- and 24 h following injection of ^99mTc-anti-TNF. Segmentation of lung regions and ^99mTc-anti-TNF activity quantification was undertaken using novel semi-automated and AI-driven approaches.

A significant increase in normalised activity, representing increased TNF inflammatory activity, was seen between the two time-points in the COPD group (mean±sd: 64.88±31.04%, p=0.029) and not in healthy controls (35.38±34.33%, p=0.110). However, analysis at a single time-point revealed higher normalised activity in the healthy group. We demonstrated that pulmonary blood vessel density and degree of emphysema were strongly correlated with this activity signal and identified as confounding factors, highlighting the need to address differences in target-organ characteristics in COPD. Experimental methods to adjust for these factors were developed for organ-specific signal quantification.

We report novel analysis techniques for molecular imaging of the human lung, presenting a platform which provides new insights into complex inflammatory disease and future precision medicine approaches.