Developing Technetium radiochemistry to assess bisphosphonate-antibiotic conjugate biodistribution

The effective antimicrobial treatment of bone infections / osteomyelitis are often hampered by the secretion of beta-lactamase enzymes that inactivate the beta-lactam ring of otherwise effective penicillins and related antibiotics. To neutralize enzyme activity, beta-lactam antibiotics will often be co-administered with beta-lactamase inhibitors, such as Tazobactam. However, the systemic introduction of beta-lactamase inhibitors may not always lead to optimal bone tissue bioavailability – the desired site of action for treating bone infections such as osteomyelitis. Herein, we target the beta-lactamase inhibitor Tazobactam directly to bone by conjugation to a bisphosphonate (BP) carrier.
The graduate student will now travel for a 3 month internship in a collaborator’s lab in Japan, and will be trained in radiolabeling chemistry capable of measuring the biodistribution of the drug after injection into lab rats. Our research outcomes will provide the evidence necessary for indication of these novel platform of bone-seeking antimicrobial compounds in the treatment of bone infections such as osteomyelitis associated with arthroplasty revision surgery. Uptake by knowledge users (orthopaedic surgeons, infectious disease pharmacists) will significantly improve effective antimicrobial therapy and help reduce kidney and liver toxicity in the antimicrobial treatment these patients.

Faculty Supervisor:

Michael Doschak

Student:

Partner:

Chiba University

Discipline:

Life Sciences

Sector:

Biotechnology; Health and Related Sciences & Technology; Biomanufacturing

University:

University of Alberta

Program: