Evaluation of a Novel Infection PET Diagnostic

Project Summary Abstract Bacterial infections such as those of prosthetic jointsbonesosteomyelitisand heart valvesinfective endocarditisare difficult to difficult to diagnose and treatand are a major cause of mortalitymorbidity and health care costsThe long term goal of our program is thus to develop positron emission tomographyPETradiotracers that can be used for non invasive PET imaging to detect and localize bacterial pathogens in humansSuch radiotracers will distinguish between different pathogen populationsserve as non invasive diagnostics and inform on bacterial load during chemotherapythereby identifying and improving treatment of patients with infectious diseasesWe have synthesized a fluorinelabeled derivate of p aminobenzoic acidfluoroaminobenzoic acidF F PABAa novel radiotracer that is selectively taken up by bacteria including clinicallyrelevant strains of Saureus including MRSAWe have shown thatF F PABA accumulates at the site of Saureus infection in an animal model of diseaseand can quantify bacterial load as a function of chemotherapySignificantlyF F PABA can distinguish bacterial infection from inflammation unlike the widely used clinical PET tracerdeoxyF fluoro D glucoseF FDGThe object of this Phase I STTR is to validateF FPABA in a preclinical model of infection and perform studies in preparation for an IND submissionIn Aimwe will demonstrate thatF F PABA can detect and image Saureus in a preclinical model of periprosthetic joint infection and that this radiotracer can quantify bacterial load as a function of antibiotic treatmentIn Aimwe will perform dosimetry studies in order to assess the radiation exposure caused by a projected human doseWe will also demonstrate thatF PABA does not display any adverse effects attimes the projected human dose in miceThuswe will show that radiation burden and toxicity resulting from the dose of radiotracer proposed for clinical studies is within the acceptable range based on data from the FDAWe have already developed a cGMP synthesis ofF F PABA suitable for human studiesand this Phase I STTR will pave the way for a Phase II STTR in which we will translate the radiotracer into humans Project Narrative Many human bacterial infections including those of prosthetic jointsare difficult to detect and treat due to their location in the human body and are a serious cause of morbidity and health care costsTo meet this unmet medical needwe will validate a radiotracer that can detect and localize bacterial pathogens in humans using non invasive positron emission tomography imagingThis radiotracer can distinguish between different pathogen populationsserve as non invasive diagnostic and inform on bacterial load during chemotherapythereby identifying and improving treatment of patients with infectious diseases