title: Nuclear imaging: a powerful novel approach for tuberculosis.
abstract: Nearly 20 years after the World Health Organization declared tuberculosis (TB) a global public health emergency, TB still remains a major global threat with 8.6 million new cases and 1.3 million deaths annually. Mycobacterium tuberculosis adapts to a quiescent physiological state, and is notable for complex interaction with the host, producing poorly-understood disease states ranging from latent infection to fully active disease. Of the approximately 2.5 billion people latently infected with M. tuberculosis, many will develop reactivation disease (relapse), years after the initial infection. While progress has been made on some fronts, the alarming spread of multidrug-resistant, extensively drug-resistant, and more recently totally-drug resistant strains is of grave concern. New tools are urgently needed for rapidly diagnosing TB, monitoring TB treatments and to allow unique insights into disease pathogenesis. Nuclear bioimaging is a powerful, noninvasive tool that can rapidly provide three-dimensional views of disease processes deep within the body and conduct noninvasive longitudinal assessments of the same patient. In this review, we discuss the application of nuclear bioimaging to TB, including the current state of the field, considerations for radioprobe development, study of TB drug pharmacokinetics in infected tissues, and areas of research and clinical needs that could be addressed by nuclear bioimaging. These technologies are an emerging field of research, overcome several fundamental limitations of current tools, and will have a broad impact on both basic research and patient care. Beyond diagnosis and monitoring disease, these technologies will also allow unique insights into understanding disease pathogenesis; and expedite bench-to-bedside translation of new therapeutics. Finally, since molecular imaging is readily available for humans, validated tracers will become valuable tools for clinical applications.
authors.affiliation: NIAID/NIH, Bethesda, MD. Electronic address: daniel.johnson@nih.gov.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Johnson
authors.affiliation: NIAID/NIH, Bethesda, MD.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.affiliation: NIAID/NIH, Bethesda, MD.
authors.forename: Peter
authors.initials: P
authors.lastname: Kim
authors.affiliation: Aeras, Rockville MD.
authors.forename: Dominick
authors.initials: D
authors.lastname: Laddy
authors.affiliation: NIAID/NIH, Bethesda, MD.
authors.forename: Chuen-Yen
authors.initials: CY
authors.lastname: Lau
authors.affiliation: FDA/CDER, Silver Spring, MD.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Weinstein
authors.affiliation: Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
mesh_terms: D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D009683:Nuclear Medicine; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology
keywords: Drug-resistance; PET; Pharmacokinetics; Probe-design; SPECT