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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how [11C]trimethoprim, a new imaging tool, can detect bacterial infections in the body. Participants will undergo PET/CT scans to observe how this compound spreads and is absorbed, aiding researchers in assessing its effectiveness. The trial divides participants into two groups: one focuses on the compound's overall distribution, while the other examines detailed imaging techniques. Individuals who suspect a bacterial infection and have not recently used trimethoprim antibiotics may be suitable for this study.

As a Phase 1 trial, participants will be among the first to help researchers understand how this new imaging tool functions in people.

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 prior data suggests that 11C-Trimethoprim imaging is safe for detecting bacterial infections?

Research has shown that 11C-Trimethoprim is generally safe for people. This compound is based on trimethoprim, a well-known antibiotic. Studies have identified it as a small, man-made molecule with various applications. It has been used in imaging studies to detect both regular and drug-resistant bacterial infections. These studies reported no major safety issues, suggesting that 11C-Trimethoprim is well-tolerated for imaging in humans. However, the current trial, still in its early stages, primarily focuses on determining the safety and optimal dosage for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 11C-Trimethoprim imaging for bacterial infections because it offers a novel way to visualize and diagnose infections in the body using PET/CT scans. Unlike traditional methods that rely on blood tests or physical symptoms to identify bacterial infections, this technique directly images the infection site, providing precise and immediate insight. This innovative approach could lead to faster and more accurate diagnoses, potentially improving treatment outcomes by allowing for more targeted therapies. Additionally, by observing how 11C-Trimethoprim is distributed in the body, researchers can gather valuable information on the effectiveness of treatments in real-time, potentially revolutionizing how infections are monitored and managed.

What evidence suggests that 11C-Trimethoprim imaging is effective for detecting bacterial infections?

Research has shown that 11C-Trimethoprim is a promising tool for imaging bacterial infections. In lab studies, both regular and drug-resistant bacteria absorbed this substance well. This finding suggests it could help doctors identify infections that might not respond to usual antibiotics. Early tests indicate it can detect many types of bacterial infections, potentially offering a new way to diagnose these conditions accurately. By highlighting where bacteria are present, it could guide more effective treatments. Participants in this trial will join either the Biodistribution or Dynamic cohort, both utilizing 11C-Trimethoprim PET/CT scans to study its effectiveness in imaging bacterial infections. ^{2 3 4 5 6}

Who Is on the Research Team?

David Mankoff, MD PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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.

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

(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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9479701/

Imaging sensitive and drug-resistant bacterial infection with ... Using a PET radiotracer based on the antibiotic trimethoprim (TMP), [ 11 C]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03424525

Study Details | NCT03424525 | 11C-Trimethoprim PET/CT ... [11C]TMP is a radiolabeled imaging agent for positron emission tomography (PET/CT). Most relevant to this protocol, it is for imaging bacterial infection in ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36106638/

Imaging sensitive and drug-resistant bacterial infection with ... Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One ...

4. medrxiv.org medrxiv.org/content/10.1101/2021.09.21.21262899.full

Imaging Sensitive and Drug-Resistant Bacterial Infection ... The PET radiotracer [ 11 C]-trimethoprim shows high uptake in both TMP-sensitive and -resistant bacteria in vitro, the potential for imaging many different ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/60/supplement_1/1642

First-in-human biodistribution and dosimetry of [11C ... The purpose of this protocol to evaluate the first-in-human biodistribution and dosimetry of uptake of [ 11 C]TMP in human subjects with PET/CT.

6. jci.org jci.org/articles/view/156679

Imaging sensitive and drug-resistant bacterial infection with ... This work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis.