Detection of Radiolabeled Inflammatory Cell Macrophage Subpopulations in Chronic Respiratory Diseases: Results from
Abjal Pasha Shaik1, Asma Sultana Shaik2, Manal Abudawood1,3
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
Abstract:
Chronic respiratory diseases (CRDs) like asthma and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Alveolar macrophages (AM) are immune cells that exist in different polarization states/phenotypes and have been shown to play a critical role during an inflammatory process. In this paper, differently polarized mouse bone marrow-derived macrophages (BMDM (M1-proinflammatory or M2-immunomodulator)) were radiolabeled with either 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO), 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), or 67Ga-citrate. Biocompatibility and in vivo biodistribution of radionuclide-labeled macrophages after intravenous injection were evaluated. Radioactivity measurements were performed using Packard Cobra Quantum 5002 Gamma Counter. Both M1 and M2 macrophages showed a higher uptake for 18F-FDG and 99mTc-HMPAO, than 67Ga-citrate. M2 macrophages showed a higher uptake of radionuclides than M1 macrophages. The used radionuclides were biocompatible for both M1 and M2 macrophages. At 2-hour postinjection, 18F-FDG-labeled M1 and M2 macrophages were found significantly higher in the lung of inflammatory animals (12.54 ± 1.58% and 14.13 ± 1.03%, respectively) than in control mice. Labeling macrophages with either 18F-FDG or 99mTc-HMPAO did not affect their biodistribution. The results from these initial experiments indicate that radionuclide-labeled macrophages may allow a higher sensitivity detection in nuclear imaging techniques such as PET and SPECT. Further confirmatory studies are needed to noninvasively image radiolabeled BMDM to understand their role in the inflammatory processes inherent to CRDs.
Insights
Radionuclide-labeled macrophages show promise for imaging chronic respiratory diseases. This study found 18F-FDG and 99mTc-HMPAO effectively labeled macrophages, with higher lung uptake in inflammatory models, suggesting potential for advanced nuclear imaging.
Area of Science:
- Immunology and Nuclear Medicine
- Investigating immune cell behavior in respiratory disease models using radiolabeling techniques.
Background:
- Chronic respiratory diseases (CRDs) like asthma and COPD are leading global causes of illness and death.
- Alveolar macrophages (AMs) are key immune cells with diverse polarization states (M1, M2) crucial in inflammatory processes.
Purpose of the Study:
- To evaluate the biocompatibility and biodistribution of differently polarized mouse bone marrow-derived macrophages (BMDM) labeled with various radionuclides.
- To assess the potential of radionuclide-labeled macrophages for non-invasive imaging in CRD-related inflammation.
Main Methods:
- Mouse bone marrow-derived macrophages (M1 and M2 phenotypes) were radiolabeled with 99mTc-HMPAO, 18F-FDG, or 67Ga-citrate.
- Biocompatibility and in vivo biodistribution were assessed after intravenous injection in control and inflammatory animal models.
- Radioactivity was measured using a Packard Cobra Quantum 5002 Gamma Counter.
Main Results:
- Both M1 and M2 macrophages exhibited higher uptake of 18F-FDG and 99mTc-HMPAO compared to 67Ga-citrate.
- M2 macrophages showed greater radionuclide uptake than M1 macrophages; labeling did not compromise macrophage biocompatibility.
- 18F-FDG-labeled M1 and M2 macrophages demonstrated significantly higher lung accumulation in inflammatory models versus controls at 2 hours post-injection.
Conclusions:
- Radionuclide labeling of BMDM with 18F-FDG or 99mTc-HMPAO is biocompatible and does not alter biodistribution.
- The findings suggest that radiolabeled macrophages could enhance detection sensitivity in nuclear imaging techniques like PET and SPECT.
- Further research is warranted to validate non-invasive imaging of radiolabeled BMDM for understanding their role in CRD inflammation.
