Tuberculosis (TB) disease affects 10 million people worldwide every year and is the leading cause of death from an infectious disease. New TB biomarkers are required for a variety of applications, including detection of sub-clinical disease for early intervention to prevent disease progression; detection of new active TB cases; and for monitoring of treatment response in clinical practice or in clinical trials of new TB therapies. A good option could be PET imaging.
Positron emission tomography (PET) imaging in combination with structural imaging may have value as a biomarker for detecting subclinical TB disease, an active disease where the diagnosis is problematical, and an outcome measure in clinical trials. The standard PET ligand, [18F]fluoro-2-deoxy-2-D-glucose (FDG), accumulates in cells with high levels of glucose metabolism and is a non-specific marker of inflammation. There may be additional value in using alternatives to FDG if these have higher sensitivity or specificity for TB-infected cells.
Somatostatin analog PET imaging radiotracers are useful in evaluating neuro-endocrine tumors and other cancers’ cells that have upregulated cell surface somatostatin receptors (SSTRs). These receptors are also overexpressed on activated macrophages, which are a key cell population infected by TB, residing within granulomas. Over-expression of somatostatin receptors in granulomas within lymph nodes of TB patients have been visualized using in vitro autoradiography, and SSTR-positive cells have been detected using immunohistochemistry analysis in granulomas from multiple granulomatous conditions including pulmonary nodules in TB.