[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

Trial Summary

What is the purpose of this trial?

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 infection using an imaging procedure called Positron Emission Tomography/Computed Tomography (PET/CT).

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 data supports the effectiveness of the drug [18F]Fluoropropyl-Trimethoprim for imaging bacterial infections?

Research shows that [18F]Fluoropropyl-Trimethoprim can effectively identify live bacterial infections, such as those caused by Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with high specificity and low background noise in important tissues. This suggests it could be a useful tool for accurately detecting bacterial infections. ^{1 2 3 4 5}

Is [18F]F-TMP PET/CT Imaging for Bacterial Infections safe for humans?

The research articles do not provide specific safety data for [18F]F-TMP PET/CT Imaging or its related compounds in humans. ^{6 7 8 9 10}

How is [18F]F-TMP PET/CT imaging different from other treatments for bacterial infections?

[18F]F-TMP PET/CT imaging is unique because it uses a PET scan with a special tracer based on the antibiotic trimethoprim to specifically detect live bacterial infections, distinguishing them from other conditions like inflammation or cancer. This method offers a more accurate way to identify bacterial infections without interference from other types of tissue changes. ^{1 2 3 11 12}

Research Team

Daniel Pryma, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

Synthesis and evaluation of a [18F]formyl-Met-Leu-Phe derivative: A positron emission tomography imaging probe for bacterial infections. [2019]

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

Synthesis and biological evaluation of N-(2-[(18)F]Fluoropropionyl)-L-methionine for tumor imaging. [2016]

5. China pubmed.ncbi.nlm.nih.gov

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

6. Netherlands 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. [2013]

7. Switzerland 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics. [2019]

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

Trimethoprim: clinical use and pharmacokinetics. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives. [2017]

11. Germany pubmed.ncbi.nlm.nih.gov

In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET. [2019]

12. United States 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. [2018]