PET imaging agents for bacterial imaging in people
There is an unmet clinical need for improved detection of pathologic bacteria in humans and animals. More specifically, there must be better imaging agents for distinguishing bacterial infection from non-specific inflammation or cancer, all of which can have a similar appearance using traditional contrast-enhanced anatomic imaging. Nuclear medicine SPECT techniques such as WBC or gallium scanning are limited by spatial resolution and imaging sensitivity. Furthermore, these current techniques rely on secondary sequelae of bacterial infection rather than binding the bacteria directly, which could allow for quantitative measurement of infection severity.
Penn researchers have developed PET radiochemical modifications of a widely used and approved antibiotic trimethoprim (TMP), which can be used for diagnostic imaging of bacteria. TMP has high affinity and specificity for E. coli dihydrofolate reductase enzyme (Ec-DHFR), a bacterial protein that is highly genetically conserved across many bacterial species. [11C]TMP can be quickly translated into patients (same molecular structure as the antibiotic) and [18F]FPTMP has a 110 minute half-life, which allows better signal to noise (can be distributed to community hospitals by a regional radiopharmacy).
Our compounds show high signal to noise ratio in an in vivo mouse model. The possibilities are far-reaching. For example, they can be used in determining the extent of osteomyelitis in a diabetic patient prior to amputation, stratifying the bacterial load in the lungs of a cystic fibrosis child, and distinguishing a benign bacterial/infectious process in the lungs of a lung cancer patient from a deadly new metastasis. Ultimately, these radiotracers can reduce needless surgical biopsies and inappropriate use of antibiotics, especially crucial in the era of modern precision medicine.
- High yield, inexpensive, simple, automated method of synthesis
- High signal-to-noise ratio
- High specificity for Ec-DHFR even at low concentration of the radiotracer
- Novel synthesis method for [18F]FPTMP which includes use of unique linker
- Potentially faster track to clinical trials as TMP is approved and widely used in the clinic
- Distinguishing bacterial infection from bland inflammation or cancer
- Diagnosing and illustrating the extent of osteomyelitis
- Reducing biopsies or unneeded surgery
- Evaluating fever of unknown origin or possible orthopedic hardware infection.
- Determining infected abscess versus seroma in a post operative patient
- Evaluating partially treated/chronic infection and determining response to antibacterial therapy
Stage of Development:
In vivo (mouse) data
Sellmyer et al. J Nucl Med, 2015
Docket # 15-7528