Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Abstract

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer.

Retention of 64Cu-FLFLF, a Formyl Peptide Receptor 1-Specific PET Probe, Correlates with Macrophage and Neutrophil Abundance in Lung Granulomas from Cynomolgus Macaques

“…Alternative approaches including intravascular addition of fluorochrome-labeled antibodies before necropsy, as has been done for macaques with TB, have promise but are limited by an inability to visualize granuloma dynamics over the course of disease. This obstacle could be overcome by incubating isolated neutrophils with a PET tracer before returning them to circulation, as has been done with neutrophils labeled for SPECT imaging in nonsmall cell lung cancer patients . This labor-intensive procedure carries a risk of exogenously activating the neutrophils, thus an approach using a neutrophil-specific probe would alleviate this concern.…”

“…This obstacle could be overcome by incubating isolated neutrophils with a PET tracer before returning them to circulation, as has been done with neutrophils labeled for SPECT imaging in nonsmall cell lung cancer patients. 66 This labor-intensive procedure carries a risk of exogenously activating the neutrophils, thus an approach using a neutrophil-specific probe would alleviate this concern. Future efforts in this area, identifying highly expressed neutrophil surface proteins or probes that can be selectively taken up by neutrophils and delivery systems with favorable physiologic profiles, will improve our understanding of how neutrophils influence TB progression at the local and systemic levels.…”

The Liver Pre-Metastatic Niche in Pancreatic Cancer: A Potential Opportunity for Intervention

“…Along similar lines, Farahi et al demonstrated that 111 In-tropolonate can be used to radiolabel patient-derived neutrophils and track them while they home into lung tumors using SPECT-CT [ 93 ]. Given the involvement of neutrophils in pre-metastatic niche formation, such an approach may be applicable for its detection.…”

Neutrophils in secondary lymphoid organs

“…Human and murine studies have demonstrated that neutrophils contribute to inflammation in the tumour microenvironment and systemically. In human lung cancer, radiolabelled neutrophils trafficked from blood into tumour tissues in vivo [ 84 ], and tumour‐associated neutrophils (TANs) comprised up to 25% of isolated tumour cells [ 85 ]. Murine TANs have been shown to exhibit both anti‐tumour (N1) and pro‐tumour (N2) phenotypes, with TGF‐β driving a pro‐tumour phenotype [ 86 ]; however, the relationship between anti‐tumour TANs and the aforementioned polymorphonuclear‐myeloid derived suppressor cells (PMN‐MDSCs) remain incompletely understood.…”