Assessment of [18F]-Fluorocellobiose ([18F]FCB) Pharmacokinetics in Healthy Volunteers and Subjects With Invasive Mold Infections

Phase 1 Clinical Trial for The Assessment Of [18F]-Fluorocellobiose ([18F]FCB) Pharmacokinetics in Healthy Volunteers and Subjects With Invasive Mold Infections

Background:

Fungal infections can cause serious disease in the lungs and other parts of the body. About 3.8 million people die with fungal infections each year. Currently, there is no way to find fungal infections in the body using imaging scans. Researchers want to see if a new tracer (a radioactive drug that collects in certain body tissues) can help find fungal infections using positron emission tomography (PET)/computed tomography (CT) scans.

Objective:

To test a new tracer ([18F]Fluorocellobiose) for PET/CT scans in people with and without fungal infections.

Eligibility:

People aged 18 years and older who have fungal infections. Healthy volunteers are also needed.

Design:

Participants will have 3 clinic visits.

The first visit will be for screening. Participants will have a physical exam with blood tests and a test of their heart function.

The second visit will be for PET/CT scanning. A thin tube called a catheter will be inserted into a vein in the arm. The study tracer will be given through the catheter. For the scans, participants will lie on a padded bed that slides through a donut-shaped machine. The machine will take pictures of the inside of the body from the head to the upper thighs. Some participants will have only 1 scan; others will have 2 scans. The second scan will be about 90 minutes after the first one.

The third visit will be for repeat blood and urine tests.

Study Description:

This study is intended to assess the pharmacokinetics (distribution, metabolism and excretion) of the novel PET radiopharmaceutical [18F]FCB in healthy individuals and to evaluate whether radioactive signal accumulation will be seen in individuals with certain fungal infection after [18F]FCB injection

Objectives:

Primary:

-To evaluate uptake of [18F]FCB in subjects with invasive fungal infections

Secondary:

• To study the pharmacokinetics and radiation dosimetry of [18F]FCB in healthy volunteers
• To establish the safety of [18F]FCB in healthy volunteers and in subjects with mold infections

Endpoints:

Primary:

-Standardized uptake values (SUV) values from the site of suspected fungal infection after injection of [18F]FCB

Secondary:

-SUV values from various organs after injection of [18F]FCB, Organ time-activity curves (from dynamic data 1-60 minutes after injection), Radiation dose to organs of the body, Safety evaluation tests

• INCLUSION CRITERIA:

Inclusion Criteria for healthy volunteers (Groups 1 and 2)

1. Male or female >=18 years of age at the time of consent and imaging.
2. Provision of signed and dated informed consent form.
3. Subjects must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures. Adults lacking capacity will not be enrolled in this study.
4. Stated willingness to comply with all study procedures and availability for the duration of the study.
5. Generally healthy subjects based on medical history, physical examination, and laboratory testing, as determined by the PI.
6. Female participants of childbearing potential must be using a medically acceptable means of contraception.

Inclusion Criteria for Patients with PROVEN or PROBABLE Aspergillosis or Mucormycosis Infections (Groups 3a and 3b)

1. Male or female >=18 years of age at the time of consent and imaging.
2. Provision of signed and dated informed consent form.
3. Subjects must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures. Adults lacking capacity will not be enrolled in this study.
4. Stated willingness to comply with all study procedures and availability for the duration of the study.
5. PROVEN or PROBABLE Invasive fungal disease (IFI), defined by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) [18].
6. Female participants of childbearing potential must be using a medically acceptable means of contraception.

For inpatients, they should be determined by the attending of record to be stable to participate in the study (will be documented in the research records).

Inclusion Criteria for Participants with Non-Aspergillus/Non-Mucorales Mold Infections (Group 4a) and Participants with Dimorphic Fungal Infections (Group 4b).

1. Male or female >=18 years of age at the time of consent and imaging.
2. Provision of signed and dated informed consent form.
3. Subjects must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures. Adults lacking capacity will not be enrolled in this study.
4. Stated willingness to comply with all study procedures and availability for the duration of the study.
5. Non-Aspergillus/non-Mucorales mold infections including, but not limited to Cladophialophora spp., Dematiaceous molds (such as Curvularia, Scedosporium spp.) or dimorphic fungi (including, but not limited to Blastomyces spp., Coccidioides spp., Histoplasma spp. and Exophiala spp.).
6. Female participants of childbearing potential must be using a medically acceptable means of contraception.

For inpatients, they should be determined by the attending of record to be stable to participate in the study (will be documented in the research records).

Acceptable effective method of contraception (birth control) will include:

• Partner vasectomy (making sterile)
• Bilateral tubal ligation
• Intrauterine devices (IUDs)
• Hormonal implants (such as Implanon)
• Other hormonal methods (birth control pills, injections, patches, vaginal rings)

EXCLUSION CRITERIA:

Exclusion Criteria for healthy subjects (Groups 1 and 2)

Complete medical records will be reviewed, and within 1-3 months prior to the planned imaging, a complete blood count with differential and blood comprehensive metabolic panel will be performed. Subjects will be excluded from enrollment if any of the following apply:

1. Clinically significant abnormalities on EKG or laboratory testing (blood and urine tests) as judged by the principal investigator.
2. Reported pregnancy or pregnancy as determined by positive or indeterminate serum human Chorionic Gonadotrophin (hCG) or urine pregnancy tests prior to radiopharmaceutical dosing.
3. Lactating females.
4. History of uncontrolled diabetes mellitus.
5. Lack of adequate venous access.
6. Previous nuclear imaging or therapy administered within 5 physical half-lives of the used radioisotope prior to study enrollment.
7. Inability to lie flat on the PET/CT bed for the planned duration of scan, including claustrophobia and weight greater than the maximum for the scanner (500 lbs).
8. NIH employee who is a subordinate/relative/co-worker of the investigators.

Exclusion Criteria for with PROVEN or PROBABLE Aspergillosis or Mucormycosis infections (Groups 3a and 3b) and non-Aspergillus/non-Mucorales mold (Group 4a) or dimorphic fungal infections (Group 4b)

Complete medical records will be reviewed, and within 28 days prior to imaging, a complete blood count with differential and blood comprehensive metabolic panel will be performed (unless already performed by the referring team as part of clinical evaluation). Subjects will be excluded from enrollment if any of the following apply:

1. Abnormalities on laboratory testing judged by the principal investigator to affect the reliability or safe performance of the scan.
2. Participants with severe hepatic and/or renal failure as determined by the primary clinical team
3. Reported pregnancy or pregnancy as determined by positive or indeterminate serum human chorionic gonadotrophin (hCG) or urine pregnancy tests prior to radiopharmaceutical dosing.
4. Lactating females.
5. History of uncontrolled diabetes mellitus.
6. Lack of adequate venous access.
7. Previous administration of a radioisotope within 5 physical half-lives prior to study enrollment.
8. Inability to lie flat on the PET/CT bed for the planned duration of scan, including claustrophobia and weight greater than the maximum for the scanner (500 lbs).