Site-Specific Detection of Latent Tuberculosis Through Nuclear Imaging
Abstract
Fiscal Year 2018 Peer Reviewed Medical Research Program Topic Area: Tuberculosis Problem: Since antiquity, tuberculosis (TB) has remained a global threat and even more so in the modern age with the emergence of diseases such as acquired immune deficiency syndrome (AIDS) that makes TB the number one killer in such groups. The threat to military forces also remains high due to deployments overseas in countries with poor health care. The presence of latent forms of TB, which remain hidden from regular laboratory tests, also complicates diagnosis and administration of timely treatment. Routine and indiscriminately used antibiotics typically leads to development of antibiotic resistance. To complicate matters further, in a significant number of patients, infections persist and spread to deeper areas in the body or, in some cases, infections return, causing considerable pain, require extended periods of recovery, high costs of treatment and even death. Therefore, newer and advanced strategies are needed to swiftly and accurately identify the hidden pathogens causing the infection. This information would potentially inform the treating physician(s) about the presence, location, spread, and burden of the pathogen(s) and help in timely treatment and prescribing the right antibiotics. Our Proposed Solution: Nuclear imaging is a form of noninvasive medical imaging that provides unique insights into the events occurring in the body at the molecular and cellular level, thereby enabling physicians to personalize patient care. It involves injecting small amounts of radioactive metals, often attached to a molecule and collectively known as a “probe” that targets the cells of interest in the body. Currently, various probes are used in the clinics, but they are only able to tell whether there is an infection or not, and also they are unable to distinguish between infection and inflammation, which could be caused by a variety of diseases. We propose to develop a novel probe that will not only be able to distinguish between infection and inflammation, but also importantly be able to accurately identify the type of pathogen causing the infection. Our method is also very versatile as the same probes can be used to rapidly screen patient samples in point-of-care devices as well as be injected into patients for whole body imaging to track the hidden pathogens. We will accomplish this objective by employing small molecules secreted by bacteria that are known to bind to metals. These metal binding molecules are unique to different types of bacterial pathogens, including TB-causing bacteria. We will attach a radioactive metal to these molecules using a simple reaction and inject them intravenously to target bacteria that were previously introduced in mice at specific locations. We expect these unique probes to travel unhindered in the body of these animals and label the pathogenic bacteria wherever they are located. Innovation: This project seeks to find a new approach to accurately identify bacterial pathogens in the body. It also defines a new role for the metal binding molecules secreted by bacteria as imaging agent for nuclear imaging. Compared to traditional techniques used to manufacture probes, this strategy seeks to simplify the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Also, in contrast to existing probes, this technique will be able to label “live” TB-causing bacteria inside the body and image them in real time. Impact: The short-term impact of this project will be on enabling swift, early, and accurate diagnosis of hidden TB infection, which is expected to shorten the course of infectious disease, decrease associated disability, and reduce hospitalization time and total cost of treatment. We also anticipate that such knowledge will be used to help reduce the inappropriate use of antibiotics for treatment and eventually prevent the develo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910125
Entities
People
- Nalinikanth Kotagiri
Organizations
- United States Army
- University of Cincinnati