11C-Trimethoprim PET/CT Imaging to Evaluate Biodistribution and Kinetics in Human Subjects

11C-Trimethoprim PET/CT Imaging to Evaluate Biodistribution and Kinetics in Human

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: 11C-Trimethoprim

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Inclusion Criteria at least 18 years of age
2. Known or suspected bacterial infection.
3. 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:

1. Antibiotic therapy with trimethoprim within 48h of the baseline PET/CT scan.
2. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
3. 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.
4. Females who are pregnant or breast feeding 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biodistribution; 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.	Drug: 11C-Trimethoprim; [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 human subjects. TMP is well-known, safe, broad-spectrum, synthetic, small molecule antibiotic that has been used clinically for over 50 years for the treatment of acute bacterial infection and has been combined with sulfa-based antibiotics (Bactrim/Septra) for bacterial infection prophylaxis especially in the lung and bladder.
Experimental: Dynamic; 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.	Drug: 11C-Trimethoprim; [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 human subjects. TMP is well-known, safe, broad-spectrum, synthetic, small molecule antibiotic that has been used clinically for over 50 years for the treatment of acute bacterial infection and has been combined with sulfa-based antibiotics (Bactrim/Septra) for bacterial infection prophylaxis especially in the lung and bladder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kinetics of uptake of [11C]TMP in human patients	The biodistribution which includes kinetics of uptake of [11C]TMP in human patients via PET/CT will be measured	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[11C]trimethoprim in infected versus non-infected tissues	Measure uptake of [11C]trimethoprim in infected versus non-infected tissues via PET/CT	3 years
The change in biodistribution which includes kinetics of uptake of [11C]TMP in human patients after therapy	Describe the change in biodistribution which incldues kinetics of uptake of [11C]TMP in human via PET/CT	3 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: David Mankoff, MD PhD, University of Pennsylvania

Publications and helpful links

General Publications

• Lee IK, Jacome DA, Cho JK, Tu V, Young AJ, Dominguez T, Northrup JD, Etersque JM, Lee HS, Ruff A, Aklilu O, Bittinger K, Glaser LJ, Dorgan D, Hadjiliadis D, Kohli RM, Mach RH, Mankoff DA, Doot RK, Sellmyer MA. Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim. J Clin Invest. 2022 Sep 15;132(18):e156679. doi: 10.1172/JCI156679.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): October 17, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 7, 2018

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Cytochrome P-450 CYP2C8 Inhibitors; Trimethoprim
• Other Study ID Numbers: 827333

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No