CD8+ T-cell PET/CT Imaging in COVID-19 Patients (Tangelo)

[89Zr]Df-IAB22M2C Anti-CD8 Minibody PET/CT Imaging to Assess the in Vivo Distribution of CD8+ T-cells in COVID-19 Patients

A subset of patients diagnosed with severe acute respiratory syndrome (SARS)-CoV2 infection present with lymphopenia. The degree of lymphopenia, and in particular reduced cluster of differentiation (CD)8+ T-cell numbers, is correlated with clinical deterioration and intensive care unit (ICU) admission. The underlying reasons for lymphopenia in coronavirus disease (COVID)-19 is currently unclear, We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV2 presenting with lymphopenia or with normal lymphocyte counts, using Zirconium-89 ([89Zr])Df-IAB22M2C positron emission tomography (PET) imaging.

Study Overview

• Status: Terminated
• Conditions: PET Imaging; Lymphopenia Due to COVID-19; T-cell
• Intervention / Treatment: Diagnostic test: [89Zr]Df-IAB22M2C PET/CT scan

Detailed Description

Rationale: A subset of patients diagnosed with SARS-CoV2 infection present with lymphopenia. The degree of lymphopenia, and in particular reduced CD8+ T-cell numbers, is strongly correlated with clinical deterioration and ICU admission .

The underlying reasons for lymphopenia in COVID-19 is currently unclear, but several hypotheses have been put forward; 1) sequestration of CD8+ T-cells in peripheral tissues (e.g. lung) either during the effector phase of their lifespan or passively by local chemotactic signals, 2) accelerated maturation and apoptosis either induced by storm of inflammatory cytokines or direct infection or 3) resulting from decreased lymphopoiesis induced by reduced levels of stem cell factor. The lack of data on in vivo distribution of CD8+ T-cells hampers a more thorough understanding of this critical prognostic factor.

Aim: We aim to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Df-IAB22M2C PET/CT imaging.

Study design: This is a prospective, observational non-randomized pilot study in 20 patients with microbiologically proven SARS-CoV2 infection. All patients will undergo a whole body [89Zr]Df-IAB22M2C PET/CT scan.

Study population: Twenty patients ≥50 years of age with proven COVID-19, who are admitted to the ward will be included, patients will be stratified according to lymphocyte counts on admission to ensure an even distribution: presenting with lymphopenia (<1.0 x10e9/L) (n=10) and with lymphocyte numbers within normal range (1.0 - 3.5 x10e9/L) (n=10).

Study procedure: All patients will undergo a [89Zr]Df-IAB22M2C PET/CT scan 21-27 hours post intravenous injection of 1.5mg protein dose labelled with 37 megabecquerel (MBq) (1 mCi) 89Zr; and one additional blood sample at the day of scanning.

Primary study objective: The primary objective of this study is to assess differences in the in vivo distribution of CD8+ T-cells in patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts, using [89Zr]Df-IAB22M2C PET/CT imaging.

Secondary study objectives:

1. To assess the spatial correlation between [89Zr]Df-IAB22M2C uptake and abnormal findings on routine contrast-enhanced CT scan of the chest
2. To assess the correlation between in vivo biodistribution of [89Zr]Df-IAB22M2C and concurrent flowcytometric phenotypic and quantitative assessment of lymphocyte populations
3. To explore the correlation between in vivo biodistribution of [89Zr]Df-IAB22M2C and clinical course of disease

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population for this pilot study exists of 20 evaluable patients with a proven SARS-CoV2 infection admitted to the Infectious Diseases ward. Patients presenting in the Radboud University Medical Center will be considered for recruitment.

Description

Inclusion Criteria:

• a microbiologically proven SARS-CoV2 infection
• More than 50 years of age;
• Ability to provide written informed consent.

Exclusion Criteria:

• Contra-indication for PET: Pregnancy, Breast-feeding, Severe claustrophobia.
• Contra-indication for administration of iodine-containing contrast agents
• Other serious illness, e.g. history of malignancies or auto-immune disorders
• Known pre-existing lymphopenia from an unrelated other medical condition
• Estimated creatinine clearance ≤ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) OR oligo-uric patients (<400 mL/24hr)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
lymphopenia; lymphocyte counts (<1.0 x10e9/L)	Diagnostic test: [89Zr]Df-IAB22M2C PET/CT scan; PET imaging procedure
normal lymphocyte numbers; lymphocyte counts ((1.0 - 3.5 x10e9/L))	Diagnostic test: [89Zr]Df-IAB22M2C PET/CT scan; PET imaging procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study is to quantify uptake of [89Zr]Df-IAB22M2C, as a surrogate for the presence of CD8+ T-cells, in major organ systems of patients with proven SARS-CoV-2 presenting with lymphopenia or with normal lymphocyte counts.	The main study parameter is the SUVmean uptake of [89Zr]Df-IAB22M2C in major organs systems, e.g. lungs, spleen, bone marrow, liver and bloodpool	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Based on imaging	1) Spatial correlation of SUVmean per lung segment with CORADS score per lung segment	18 months
Based on laboratory parameters	2) In vivo biodistribution of [89Zr]Df-IAB22M2C will be correlated to laboratory test 3) In vivo biodistribution of [89Zr]Df-IAB22M2C will be correlated with lymphocyte counts (x10e9/L)	18 months
Based on clinical characteristics	4) In vivo biodistribution of [89Zr]Df-IAB22M2C will be correlated with duration of hospital stay (days)	18 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: ImaginAb, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; T-cells; PET imaging; lymphopenia
• Additional Relevant MeSH Terms: Cytopenia; Immune System Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Leukopenia; COVID-19; Lymphopenia
• Other Study ID Numbers: NL76248.091.20; 2020-005984-29 (EudraCT Number)

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No