[18F]F-TMP PET/CT Imaging for Bacterial Infections

Overseen By Erin Schubert

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Trimethoprim

Disqualifiers: Pregnancy, Severe comorbidities, others

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

Compensation: Varies

Number of Visits: 1

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging drug, [18F]Fluoropropyl-Trimethoprim, to help doctors detect bacterial infections inside the body using a PET/CT scan, a detailed body scan. The study tests how well this drug highlights areas that might have an infection. Suitable candidates for this trial include those with possible bacterial infections, as identified by their doctors or lab results. Participants will be divided into groups to observe how the drug behaves in the body during scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

If you are taking the antibiotic trimethoprim, you will need to stop it at least 48 hours before the baseline PET/CT scan. For other medications, the trial protocol does not specify any requirements.

What prior data suggests that this imaging drug is safe for use in PET/CT scans?

Research has shown that trimethoprim, the main ingredient in [18F]fluoropropyl-trimethoprim, is a well-known and safe antibiotic used in medicine for many years. However, specific safety information for [18F]fluoropropyl-trimethoprim in humans is not yet available. As an early-phase study, researchers are still learning how people handle this new imaging drug. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for bacterial infections rely on antibiotics that kill or inhibit bacteria, but [18F]Fluoropropyl-Trimethoprim offers a different approach. This novel method uses a PET/CT imaging technique to detect bacterial infections, which could dramatically improve diagnosis speed and accuracy. Unlike standard treatments, which often require a trial-and-error approach to identify the specific bacteria involved, this imaging technique can quickly highlight infection sites, potentially leading to more targeted and effective treatments. Researchers are excited because this could lead to faster recovery times and reduce the misuse of antibiotics, addressing a major public health concern.

What evidence suggests that this imaging method is effective for detecting bacterial infections?

Research has shown that [18F]Fluoropropyl-Trimethoprim ([18F]F-TMP) is a new imaging drug that helps identify bacterial infections in the body. This trial will include two separate cohorts to study the drug's effectiveness. The Biodistribution cohort will undergo a series of PET/CT scans to observe how the drug distributes in the body. Meanwhile, the Dynamic cohort will focus on dynamic scanning to assess the drug's ability to highlight infections. Early results suggest that [18F]F-TMP can specifically target bacterial infections because it is based on trimethoprim, an antibiotic that bacteria absorb. Unlike other imaging methods that might not clearly distinguish infections from other conditions, [18F]F-TMP aims to show exactly where bacteria are active, potentially helping doctors find infections more accurately. ^{1 3 6 7 8}

Who Is on the Research Team?

Daniel Pryma, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with known or suspected bacterial infections who can give informed consent. It's not for pregnant or breastfeeding women, those who've taken trimethoprim within 48 hours, people unable to undergo imaging procedures, or anyone with severe conditions that could affect their safety in the study.

Inclusion Criteria

I have or might have a bacterial infection, as indicated by tests or doctor's notes.

Able to understand 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.

Unstable or other severe medical or psychological comorbidities that would compromise the subject's safety or successful participation in the study, in the opinion of an investigator or treating physician

Inability to tolerate imaging procedures, in the opinion of an investigator or treating physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/CT scans to evaluate the biodistribution and kinetics of [18F]F-TMP

4 hours

1 visit (in-person)

Follow-up

Participants are monitored for changes in biodistribution and kinetics of [18F]F-TMP after therapy

3 years

What Are the Treatments Tested in This Trial?

Interventions

• [18F]Fluoropropyl-Trimethoprim

Trial Overview [18F]fluoropropyl-trimethoprim ([18F]F-TMP) is being tested as a radioactive tracer in PET/CT scans to see how it spreads and behaves in areas of the body with active bacterial infection.

How Is the Trial Designed?

Group I: The Dynamic cohort Experimental Treatment 1 Intervention

The Dynamic cohort will include up to 15 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 post injection of \[18F\]fluoropropyl-trimethoprim.

Group II: Biodistribution cohort Experimental Treatment 1 Intervention

The Biodistribution cohort will include up to 5 patients who will undergo a series of vertex to mid-thigh (or feet if indicated) biodistribution \[18F\]fluoropropyl-trimethoprim PET/CT scans over a period of approximately 4 hours.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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]

In a trial involving 51 women with uncomplicated urinary tract infections, fosfomycin trometamol (3 g) was more effective than trimethoprim (200 mg), achieving a 77.3% eradication rate compared to 54.5% for trimethoprim.

Both treatments were well-tolerated, with no significant adverse events reported, indicating that fosfomycin trometamol is a safe and effective alternative for treating urinary tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative double-blind randomised study of single dose fosfomycin trometamol with trimethoprim in the treatment of urinary tract infections in general practice. Harvard Davis, R., O'Dowd, TC., Holmes, W., et al.[2022]

Trimethoprim (TMP) has been marketed as a standalone treatment for common infections, highlighting its antibacterial properties and potential new clinical uses.

TMP offers advantages over TMP/sulfonamide combinations, particularly in terms of renal function and reduced toxicity, making it a safer option for patients with kidney concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimethoprim: clinical use and pharmacokinetics. Friesen, WT., Hekster, YA., Vree, TB.[2019]

6"-18F-fluoromaltotriose is a novel PET tracer that specifically targets bacterial infections by utilizing the maltodextrin transporter, distinguishing it from traditional tracers like 18F-FDG that can also accumulate in inflammatory lesions.

In studies involving various bacterial strains and a mouse model of wound infection, 6"-18F-fluoromaltotriose successfully detected bacterial presence, indicating its potential to significantly improve the diagnosis and management of bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific Imaging of Bacterial Infection Using 6″-18F-Fluoromaltotriose: A Second-Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria. Gowrishankar, G., Hardy, J., Wardak, M., et al.[2018]

A new high-performance liquid chromatography method effectively quantifies trimethoprim and its metabolites, achieving detection limits as low as 0.05-0.15 micrograms/ml, which is crucial for accurate drug monitoring.

In rat liver metabolism studies, the primary metabolic pathways for trimethoprim were identified as 3'- and 4'-hydroxylation, while the formation of TMP N-oxides was found to be a minor pathway, indicating the significance of these metabolites in drug metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of trimethoprim and its oxidative metabolites in cell culture media and microsomal incubation mixtures by high-performance liquid chromatography. van 't Klooster, GA., Kolker, HJ., Woutersen-van Nijnanten, FM., et al.[2013]

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 new PET tracer [(18)F]FPMET was successfully synthesized with a high yield of 72% and demonstrated effective transport mechanisms in cancer cells, indicating its potential for tumor imaging.

Biodistribution and PET/CT imaging studies showed that [(18)F]FPMET can effectively identify various tumors, including S180 fibrosarcoma, A549 lung adenocarcinoma, and PC-3 prostate cancer, suggesting its efficacy as a tumor imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of N-(2-[(18)F]Fluoropropionyl)-L-methionine for tumor imaging. Hu, KZ., Wang, H., Huang, T., et al.[2016]

(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]

The study found that [18F]ciprofloxacin binds rapidly and non-specifically to bacterial cells, indicating that its retention in infected tissues is not due to specific targeting of bacterial enzymes, but rather due to increased blood flow and vascular permeability associated with infection.

In PET imaging of four patients with bacterial soft tissue infections, [18F]ciprofloxacin showed increased radioactivity in infected areas compared to uninfected tissue, but the lack of specific binding means it is not suitable as a bacteria-specific imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET. Langer, O., Brunner, M., Zeitlinger, M., et al.[2019]

The newly developed 18F-labeled fMLF derivative, [18F]fMLFXYk(FB)k, shows a strong affinity for the formyl peptide receptor (FPR), making it a promising PET imaging probe for detecting bacterial infections.

In vivo studies demonstrated that this probe accumulates significantly more in infected tissues compared to non-infected areas, achieving an infection-to-muscle ratio of 4.6, which allows for clear visualization of infections within 60 minutes post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of a [18F]formyl-Met-Leu-Phe derivative: A positron emission tomography imaging probe for bacterial infections. Kimura, H., Yamauchi, S., Kawashima, H., et al.[2019]

Iodinated trimethoprim (TMP-I) demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) as low as 1.25 μg/mL, making it a promising candidate for treating MRSA infections.

The study found that halogen substitutions, particularly iodine, enhance the drug's ability to interact hydrophobically with its target, leading to improved potency compared to other TMP derivatives like diaveridine, which showed resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics. Nilchan, N., Phetsang, W., Nowwarat, T., et al.[2019]

Nineteen novel trimethoprim derivatives were synthesized and evaluated, with the most effective compound being a benzyloxy derivative (4b) that showed significantly improved antibacterial activity against Staphylococcus aureus and Escherichia coli compared to standard trimethoprim.

The study identified that certain structural modifications, particularly the introduction of benzyloxy and phenyl ethanone groups, enhanced antibacterial efficacy, while substitutions at the 4-NH2 group resulted in compounds with little to no activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives. Rashid, U., Ahmad, W., Hassan, SF., et al.[2017]

Citations

1. withpower.com withpower.com/trial/phase-1-bacterial-infections-1-2020-e5d0d

[18F]F-TMP PET/CT Imaging for Bacterial Infections The research articles do not provide specific safety data for [18F]F-TMP PET/CT Imaging or its related compounds in humans.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04263792

[18F]Fluoropropyl-Trimethoprim ([18F]F-TMP) PET/CT ... The purpose of this study is to study a radioactive tracer, a type of imaging drug that is injected into the body to see how it is taken up in sites of active ...

3. pnas.org pnas.org/doi/10.1073/pnas.1703109114

Bacterial infection imaging with [18F]fluoropropyl- ... We report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP).

4. trialx.com trialx.com/clinical-trials/listings/268370/18ffluoropropyl-trimethoprim-18ff-tmp-petct-imaging-to-evaluate-biodistribution-and-kinetics-in-human-subjects/

[18F]Fluoropropyl-Trimethoprim ([18F]F-TMP) PET/CT ... The purpose of this study is to study a radioactive tracer, a type of imaging drug that is injected into the body to see how it is taken up in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10093025/

Is Imaging Bacteria with PET a Realistic Option or an ... Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04263792

[18F]Fluoropropyl-Trimethoprim ([18F]F-TMP) PET/CT ... The parent compound, trimethoprim (TMP) is a well-known, safe, broad-spectrum, synthetic, small molecule antibiotic that has been used clinically for over 50 ...

7. clinicaltrial.be clinicaltrial.be/en/details/58141?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

[18F]Fluoropropyl-Trimethoprim ([18F]F-TMP) PET/CT ... The parent compound, trimethoprim (TMP) is a well-known, safe, broad-spectrum, synthetic, small molecule antibiotic that has been used ...

8. pubs.acs.org pubs.acs.org/doi/10.1021/acsinfecdis.8b00182

Positron Emission Tomography Imaging with 2-[ 18 F]F-p ... In a rodent myositis model, [18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other ...