11C-Trimethoprim Imaging for Bacterial Infection

Overseen By Erin Schubert, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Trimethoprim

Disqualifiers: Pregnancy, Breastfeeding, Serious comorbidities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking trimethoprim (an antibiotic) at least 48 hours before the baseline PET/CT scan. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What data supports the effectiveness of the drug 11C-Trimethoprim for imaging bacterial infections?

Research shows that 11C-Trimethoprim, a PET radiotracer based on the antibiotic trimethoprim, can effectively image bacterial infections in both drug-sensitive and drug-resistant strains. Clinical imaging demonstrated that 11C-Trimethoprim could identify areas of infection, suggesting it could help diagnose infections and monitor treatment response. ^{1 2 3 4 5}

Is 11C-Trimethoprim safe for use in humans?

Initial human studies with 11C-Trimethoprim have been conducted, demonstrating its use in imaging bacterial infections, but specific safety data for humans is not detailed in the available research. ^{1 2 5 6 7}

How does 11C-Trimethoprim differ from other drugs for bacterial infection?

11C-Trimethoprim is unique because it is a PET radiotracer that allows doctors to image bacterial infections in the body, even in cases where bacteria are resistant to antibiotics. This imaging technique helps distinguish infections from other conditions like inflammation or cancer, which is not possible with conventional imaging methods. ^{1 2 3 5 8}

What is the purpose of this trial?

Patients with suspected bacterial infection at the time screening are eligible for this study. Patients may participate in this study if they are at least 18 years of age, and most participants will be receiving care at the clinical practices of the University of Pennsylvania. Up to 30 subjects will participate in two different imaging cohorts. The Biodistribution cohort will include up to 5 patients referred from orthopedics who will undergo a series of vertex to mid-thigh (or feet if indicated) biodistribution \[11C\]trimethoprim PET/CT scans over a period of approximately 2 ½ hours. The Dynamic cohort will include up to 25 patients who will undergo approximately 60 minutes of dynamic scanning followed by up to 2 static skull base to mid-thigh (or feet if indicated) scans imaging post injection of \[11C\]trimethoprim. Some subjects who may be selected clinically to undergo surgical or antibiotic treatment may undergo a second therapy may also undergo an optional second \[11C\]trimethoprim PET/CT after the initiation of therapy to collect pilot data on the changes in \[11C\]trimethoprim biodistribution and uptake with therapy, the timing of this scan may vary depending on the type of treatment the patient is receiving. Patients will also undergo baseline lab tests complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and blood cultures. If these tests are done as part of clinical standard of care they will not need to be repeated for this study.

Research Team

David Mankoff, MD PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults with suspected bacterial infections, primarily those receiving care at the University of Pennsylvania. It's not suitable for pregnant or breastfeeding women, people who can't tolerate imaging procedures, have taken trimethoprim within 48 hours before the baseline scan, or have serious medical conditions that may affect their safety in the study.

Inclusion Criteria

I have or might have a bacterial infection.

Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria

I have taken trimethoprim within 2 days before my PET/CT scan.

Females who are pregnant or breastfeeding at the time of screening will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening.

Presence of serious or unstable medical or psychological comorbidities that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Biodistribution Imaging

Participants in the Biodistribution cohort undergo a series of vertex to mid-thigh PET/CT scans over approximately 2 ½ hours

1 day

Dynamic Imaging

Participants in the Dynamic cohort undergo approximately 60 minutes of dynamic scanning followed by up to 2 static scans post injection of [11C]trimethoprim

1 day

Follow-up

Participants are monitored for changes in biodistribution and uptake of [11C]trimethoprim after therapy

3 years

Treatment Details

Interventions

• 11C-Trimethoprim

Trial Overview The trial tests how a radioactive drug called 11C-Trimethoprim spreads and moves through the body using PET/CT scans. Participants are divided into two groups: one undergoing several scans over about 2.5 hours and another having an hour of dynamic scanning followed by up to two static scans.

Participant Groups

Group I: Dynamic Experimental Treatment 1 Intervention

The Dynamic cohort will undergo approximately 60 minutes of dynamic scanning followed by up to 2 static skull base to mid-thigh (or feet if indicated) scans imaging post injection of \[11C\]trimethoprim. Some subjects who may be selected clinically to undergo surgical or antibiotic treatment may undergo a second therapy may also undergo an optional second \[11C\]trimethoprim PET/CT after the initiation of therapy to collect pilot data on the changes in \[11C\]trimethoprim biodistribution and uptake with therapy, the timing of this scan may vary depending on the type of treatment the patient is receiving.

Group II: Biodistribution Experimental Treatment 1 Intervention

The Biodistribution cohort referred from orthopedics who will undergo a series of vertex to mid-thigh (or feet if indicated) biodistribution \[11C\]trimethoprim PET/CT scans over a period of approximately 2 ½ hours.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

The newly developed PET probe, [18F]FPTMP, shows over 100 times greater uptake in live bacteria compared to controls, indicating its potential for accurately detecting bacterial infections.

In rodent models, [18F]FPTMP successfully identified live bacterial infections without interference from other conditions like inflammation or cancer, suggesting it could be a reliable tool for distinguishing bacterial infections in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. Sellmyer, MA., Lee, I., Hou, C., et al.[2019]

The PET radiotracer [11C]-TMP showed effective uptake in both antibiotic-sensitive and resistant bacterial strains, indicating its potential for detecting infections even in the presence of antimicrobial resistance.

Clinical imaging with [11C]-TMP successfully identified infectious lesions in patients, demonstrating its feasibility as a diagnostic tool for bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim. Lee, IK., Jacome, DA., Cho, JK., et al.[2022]

(99m)Tc-labeled ciprofloxacin (CPF) shows high stability and a labeling rate over 90%, making it a reliable radiopharmaceutical for diagnosing bacterial infections in a mouse model.

The imaging results indicate that (99m)Tc-CPF has a significantly higher uptake in infected tissues compared to normal tissues, with a peak infectious tissue/normal tissue ratio of 4.30 at 4 hours post-injection, demonstrating its efficacy in identifying infection sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental studies on imaging of infected site with (99m)Tc-labeled ciprofloxacin in mice. Zhang, H., Jiang, NY., Zhu, L.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim. [2022]

3. England pubmed.ncbi.nlm.nih.gov

99m Tc-labeled antibiotics for infection diagnosis: Mechanism, action, and progress. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Current Status of SPECT Radiopharmaceuticals for Specific Bacteria Imaging. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Imaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Experimental studies on imaging of infected site with (99m)Tc-labeled ciprofloxacin in mice. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging. [2023]

8. Canada pubmed.ncbi.nlm.nih.gov

Preliminary evaluation of technetium-99m-labeled ceftriaxone: infection imaging agent for the clinical diagnosis of orthopedic infection. [2019]