Diagnostic Validity of [18F]FSPG PET for the Assessment of Acute Rejection After Heart or Liver Transplantation

NCT04488094 | Completed Phase 2

• 1 other identifier: FSPG-1902
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The a series of clinical studies of \[18F\]FSPG PET/CT showed that \[18F\]FSPG is safe and promising PET tracer for detecting inflammation with favorable biodistribution and pharmacokinetics in patients. By using \[18F\]FSPG, which targets system xCˉ, a key player in the active phase of inflammation, the goal of this phase 2 study is to evaluate diagnostic validity of \[18F\]FSPG PET/CT to detect allograft rejection after heart and liver allograft, where conventional imaging has limitations. Diagnostic efficacy of \[18F\]FSPG PET/CT will be determined in comparison with histologic evaluation of allograft biopsy. Other critical questions including whether quantitative measures of \[18F\]FSPG uptake is associated with the severity of rejection, inter-reader variability of \[18F\]FSPG PET/CT, and safety assessment will be also evaluated.

Conditions

Graft Rejection; Heart Transplantation; Liver Transplantation

Keywords

Graft Rejection; Heart Transplantation; Liver Transplantation; Positron-Emission Tomography; Diagnostic Imaging

Outcome Measures

Primary Outcomes (1)

• Sensitivity and specificity of qualitative [18F]FSPG PET/CT interpretation for the diagnosis of patients with histologic evidence of acute allograft rejection

  sensitivity = (the number of \[18F\]FSPG PET/CT-positive patients divided by the number of rejection positive patients on the histological evaluation) x 100; specificity = (the number of \[18F\]FSPG PET/CT-negative patients divided by the number of rejection negative patients on the histological evaluation) x 100

  within 7 days of [18F]FSPG PET/CT

Secondary Outcomes (8)

• Association between quantitative [18F]FSPG uptake and histologic grade of rejection

  within 7 days of [18F]FSPG PET/CT

• Inter-reader variability

  within 1 day of [18F]FSPG PET/CT

• Incidence of treatment emergent adverse events

  From the administration of [18F]FSPG to one day after [18F]FSPG PET/CT

• Blood pressure

  Pre-treatment and three hours after the administration of [18F]FSPG

• Heart rate

  Pre-treatment and three hours after the administration of [18F]FSPG

Study Arms (2)

Heart transplantation

EXPERIMENTAL

Patients suspected of having acute heart allograft rejection after heart transplantation will receive a single IV injection of \[18F\]FSPG

Drug: [18F]FSPG

Liver transplantation

EXPERIMENTAL

Patients suspected of having acute liver allograft rejection after heart transplantation will receive a single IV injection of \[18F\]FSPG

Drug: [18F]FSPG

Interventions

[18F]FSPG DRUG

A radioactive dose of 200 MBq of the study drug with a total quantity of ≤ 100 µg will be administered as slow intravenous bolus injection over up to 60 seconds. PET/CT examinations will be performed at 60-75 min after the administration of \[18F\]FSPG.

Also known as: FSPG

Heart transplantation; Liver transplantation

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is aged between 19 and 79 years and male or female of any race/ethnicity.
• Subject received heart transplantation or liver transplantation at least 30 days prior to screening
• Subject underwent or is scheduled to undergo biopsy for histologic diagnosis of acute rejection within 7 days prior to or after the planned \[18F\]FSPG PET/CT administration.

You may not qualify if:

• Subject or subject's legally acceptable representative does not provide written informed consent.
• Dose escalation of the current immunosuppressant drugs or starting a new immunosuppressant is scheduled from the study enrollment to the scheduled day of biopsy, or 24 hours after \[18F\]FSPG administration
• Subject has concurrent severe and/or uncontrolled and/or unstable medical disease (e.g. congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic renal or hepatic disease which could compromise participation in the study) in the judgment of the investigator.
• Subject is a relative of the investigator, student of the investigator or otherwise dependent.
• Subject has received any investigational drugs or devices within four weeks prior to the study enrollment or within 24 hours after administration of \[18F\]FSPG.
• Subject has been previously included in this study.
• Subject has any other condition or personal circumstances that, in the judgment of the investigator, might make collection of complete data difficult or impossible.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (4)

• Koglin N, Mueller A, Berndt M, Schmitt-Willich H, Toschi L, Stephens AW, Gekeler V, Friebe M, Dinkelborg LM. Specific PET imaging of xC- transporter activity using a (1)(8)F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clin Cancer Res. 2011 Sep 15;17(18):6000-11. doi: 10.1158/1078-0432.CCR-11-0687. Epub 2011 Jul 12.

  PMID: 21750203 BACKGROUND

• Chae SY, Choi CM, Shim TS, Park Y, Park CS, Lee HS, Lee SJ, Oh SJ, Kim SY, Baek S, Koglin N, Stephens AW, Dinkelborg LM, Moon DH. Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate PET of Inflammatory and Infectious Lesions. J Nucl Med. 2016 Jan;57(1):67-9. doi: 10.2967/jnumed.115.164020. Epub 2015 Oct 15.

  PMID: 26471694 BACKGROUND

• Baek S, Choi CM, Ahn SH, Lee JW, Gong G, Ryu JS, Oh SJ, Bacher-Stier C, Fels L, Koglin N, Hultsch C, Schatz CA, Dinkelborg LM, Mittra ES, Gambhir SS, Moon DH. Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clin Cancer Res. 2012 Oct 1;18(19):5427-37. doi: 10.1158/1078-0432.CCR-12-0214. Epub 2012 Aug 14.

  PMID: 22893629 BACKGROUND

• Baek S, Mueller A, Lim YS, Lee HC, Lee YJ, Gong G, Kim JS, Ryu JS, Oh SJ, Lee SJ, Bacher-Stier C, Fels L, Koglin N, Schatz CA, Dinkelborg LM, Moon DH. (4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. J Nucl Med. 2013 Jan;54(1):117-23. doi: 10.2967/jnumed.112.108704. Epub 2012 Dec 11.

  PMID: 23232273 BACKGROUND

MeSH Terms

Interventions

4-(3-fluoropropyl)glutamic acid

Study Officials

• Dae Hyuk Moon, MD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients suspected of having acute allograft rejection after heart transplantation (HT, n = 10) or liver transplantation (LT, n = 10)

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 27, 2020
• Study Start: November 18, 2020
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)