PET Assessment of Acute Lung Transplant Rejection

The Washington University

Status: Terminated

Conditions: Lung Disease

Treatments: Drug: [18F]FDG; Drug: [18F]ISO-1

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT02204202

R01HL121218 (U.S. NIH Grant/Contract)

1R01HL121218-01-201102155

Details and patient eligibility

About

The purpose of this research study is to gain understanding of the basic responses of the lungs to inflammation and specifically if there may be a better way to detect graft inflammation using non-invasive methods as well as to determine the effectiveness of immunosuppressive treatment regimens in preventing acute rejection in lung transplant recipients.

Full description

Positron emission tomography with fluorodeoxyglucose (FDG-PET) is a potential way we can measure lung inflammation. FDG-PET imaging is a clinically accepted and FDA-approved method that is commonly used in the diagnosis and management of cancer. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" computerized axial tomography or computed tomography (CT) scan. FDG stands for [18F] (flourine 18) fluorodeoxyglucose, a radiolabeled sugar that is used to identify areas of inflammation with the PET scanner. A CT scan takes a picture of what the lungs and airways look like.

T cells are the primary cause of acute rejection of lung transplants. Because T cells must divide in order to be activated and cause rejection, imaging them while they are dividing is another way that we can determine whether acute rejection is occurring. A new PET tracer called [18F]ISO-1 (18F-labeled σ2-receptor ligand for PET, N-(4-(6,7-dimethoxy-3,-4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-3c), binds to dividing cells. Therefore, [18F]ISO-1 may help us measure acute rejection more accurately. [18F]ISO-1 is an investigational drug.

Enrollment: 28 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Double-lung transplant recipient
• Scheduled for bronchoscopy with transbronchial biopsy
• Capable of lying still and supine with arms raised above the head within the PET/CT scanner for ~1.25 hours
• Capable of following instructions for breathing protocol during CT portion of PET/CT
• Able and willing to give informed consent
• BMI < 35
• Already scheduled to undergo bronchoscopy with bronchoalveolar lavage (BAL) for clinical reasons
• Willing to donate a portion of BAL and biopsy specimen for laboratory testing

Exclusion criteria

• Glucose level > 150 mg/dl at time of [18F]FDG PET scan (however, up to 160 mg/dl, with repeat testing showing level is stable or decreasing, is acceptable)
• Pregnancy (confirmed by qualitative urine human chorionic gonadotropin (hCG) pregnancy test)
• Lactation
• Presence of implanted electronic medical device
• Enrollment in another research study of an investigational drug
• Inability to lie flat with arms raised above the head for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT

Trial design

28 participants in 2 patient groups

Grade A0

Description:

Double-lung transplant recipients with no evidence of rejection who undergo both \[18F\]FDG and \[18F\]ISO-1 PET imaging scans

Treatment:

Drug: [18F]ISO-1

Drug: [18F]FDG

Grades A2-3

Description:

Double-lung transplant recipients with mild to moderate rejection who undergo both \[18F\]FDG and \[18F\]ISO-1 PET imaging scans

Treatment:

Drug: [18F]ISO-1

Drug: [18F]FDG