Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis

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Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer : evaluation of CD4 specificity and its potential use in collagen-induced arthritis. / Clausen, Anne Skovsbo; Christensen, Camilla; Christensen, Esben; Cold, Sigrid; Kristensen, Lotte Kellemann; Hansen, Anders Elias; Kjaer, Andreas.

In: EJNMMI Research, Vol. 12, No. 1, 62, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Clausen, AS, Christensen, C, Christensen, E, Cold, S, Kristensen, LK, Hansen, AE & Kjaer, A 2022, 'Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis', EJNMMI Research, vol. 12, no. 1, 62. https://doi.org/10.1186/s13550-022-00934-7

APA

Clausen, A. S., Christensen, C., Christensen, E., Cold, S., Kristensen, L. K., Hansen, A. E., & Kjaer, A. (2022). Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis. EJNMMI Research, 12(1), [62]. https://doi.org/10.1186/s13550-022-00934-7

Vancouver

Clausen AS, Christensen C, Christensen E, Cold S, Kristensen LK, Hansen AE et al. Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis. EJNMMI Research. 2022;12(1). 62. https://doi.org/10.1186/s13550-022-00934-7

Author

Clausen, Anne Skovsbo ; Christensen, Camilla ; Christensen, Esben ; Cold, Sigrid ; Kristensen, Lotte Kellemann ; Hansen, Anders Elias ; Kjaer, Andreas. / Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer : evaluation of CD4 specificity and its potential use in collagen-induced arthritis. In: EJNMMI Research. 2022 ; Vol. 12, No. 1.

Bibtex

@article{62c5df1c26614f2ba9644d080834b53f,
title = "Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis",
abstract = "Background CD4(+) T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4(+) T cells has potential role for early detection and monitoring of RA. Here, we developed a new radiotracer for in vivo immunoPET imaging of murine CD4(+) T cells and tested it in the collagen-induced arthritis (CIA) mouse model of human RA. Results The tracer, [Cu-64]Cu-NOTA-CD4-F(ab)'2 ([Cu-64]Cu-NOTA-CD4), was generated from F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator and radiolabeled with copper-64. Accumulation of the tracer and isotype control was evaluated in the CIA model and mice receiving whole-body irradiation (WBI) (5 Gy). The potential of [Cu-64]Cu-NOTA-CD4 for response assessment was evaluated in CIA induced mice treated with dexamethasone (DXM). Imaging data were compared with flow cytometry and immunohistochemistry (IHC) of inflammatory cells including CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 showed increased accumulation in T cell-rich tissues compared with isotype control (p < 0.0001). In addition, reduced accumulation of [Cu-64]Cu-NOTA-CD4 was observed in T cell-depleted tissue (p < 0.0001). Flow cytometry and IHC confirmed the increased infiltration of CD4(+) T cells in CIA mice. Conclusions We developed and evaluated a new radiotracer, [Cu-64]Cu-NOTA-CD4, for immunoPET imaging of murine CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 was successfully synthesized by F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to a chelator and radiolabeled with copper-64. We found that our novel CD4 PET tracer can be used for noninvasive visualization of murine CD4(+) T cells.",
keywords = "Positron emission tomography (PET), [Cu-64]Cu-NOTA-CD4, CD4(+) T cells, Rheumatoid arthritis, Collagen-induced arthritis, Animal model, POSITRON-EMISSION-TOMOGRAPHY, RHEUMATOID-ARTHRITIS, AUTOANTIGENS, IMMUNITY, THERAPY",
author = "Clausen, {Anne Skovsbo} and Camilla Christensen and Esben Christensen and Sigrid Cold and Kristensen, {Lotte Kellemann} and Hansen, {Anders Elias} and Andreas Kjaer",
year = "2022",
doi = "10.1186/s13550-022-00934-7",
language = "English",
volume = "12",
journal = "EJNMMI Research",
issn = "2191-219X",
publisher = "SpringerOpen",
number = "1",

}

RIS

TY - JOUR

T1 - Development of a Cu-64Cu-labeled CD4(+) T cell targeting PET tracer

T2 - evaluation of CD4 specificity and its potential use in collagen-induced arthritis

AU - Clausen, Anne Skovsbo

AU - Christensen, Camilla

AU - Christensen, Esben

AU - Cold, Sigrid

AU - Kristensen, Lotte Kellemann

AU - Hansen, Anders Elias

AU - Kjaer, Andreas

PY - 2022

Y1 - 2022

N2 - Background CD4(+) T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4(+) T cells has potential role for early detection and monitoring of RA. Here, we developed a new radiotracer for in vivo immunoPET imaging of murine CD4(+) T cells and tested it in the collagen-induced arthritis (CIA) mouse model of human RA. Results The tracer, [Cu-64]Cu-NOTA-CD4-F(ab)'2 ([Cu-64]Cu-NOTA-CD4), was generated from F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator and radiolabeled with copper-64. Accumulation of the tracer and isotype control was evaluated in the CIA model and mice receiving whole-body irradiation (WBI) (5 Gy). The potential of [Cu-64]Cu-NOTA-CD4 for response assessment was evaluated in CIA induced mice treated with dexamethasone (DXM). Imaging data were compared with flow cytometry and immunohistochemistry (IHC) of inflammatory cells including CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 showed increased accumulation in T cell-rich tissues compared with isotype control (p < 0.0001). In addition, reduced accumulation of [Cu-64]Cu-NOTA-CD4 was observed in T cell-depleted tissue (p < 0.0001). Flow cytometry and IHC confirmed the increased infiltration of CD4(+) T cells in CIA mice. Conclusions We developed and evaluated a new radiotracer, [Cu-64]Cu-NOTA-CD4, for immunoPET imaging of murine CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 was successfully synthesized by F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to a chelator and radiolabeled with copper-64. We found that our novel CD4 PET tracer can be used for noninvasive visualization of murine CD4(+) T cells.

AB - Background CD4(+) T cells are central inflammatory mediators in the pathogenesis of autoimmune rheumatoid arthritis (RA), as they are one of the dominating cell types in synovial inflammation. Molecular imaging of CD4(+) T cells has potential role for early detection and monitoring of RA. Here, we developed a new radiotracer for in vivo immunoPET imaging of murine CD4(+) T cells and tested it in the collagen-induced arthritis (CIA) mouse model of human RA. Results The tracer, [Cu-64]Cu-NOTA-CD4-F(ab)'2 ([Cu-64]Cu-NOTA-CD4), was generated from F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator and radiolabeled with copper-64. Accumulation of the tracer and isotype control was evaluated in the CIA model and mice receiving whole-body irradiation (WBI) (5 Gy). The potential of [Cu-64]Cu-NOTA-CD4 for response assessment was evaluated in CIA induced mice treated with dexamethasone (DXM). Imaging data were compared with flow cytometry and immunohistochemistry (IHC) of inflammatory cells including CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 showed increased accumulation in T cell-rich tissues compared with isotype control (p < 0.0001). In addition, reduced accumulation of [Cu-64]Cu-NOTA-CD4 was observed in T cell-depleted tissue (p < 0.0001). Flow cytometry and IHC confirmed the increased infiltration of CD4(+) T cells in CIA mice. Conclusions We developed and evaluated a new radiotracer, [Cu-64]Cu-NOTA-CD4, for immunoPET imaging of murine CD4(+) T cells. [Cu-64]Cu-NOTA-CD4 was successfully synthesized by F(ab)'2 fragments of R-anti-mouse CD4 antibodies conjugated to a chelator and radiolabeled with copper-64. We found that our novel CD4 PET tracer can be used for noninvasive visualization of murine CD4(+) T cells.

KW - Positron emission tomography (PET)

KW - [Cu-64]Cu-NOTA-CD4

KW - CD4(+) T cells

KW - Rheumatoid arthritis

KW - Collagen-induced arthritis

KW - Animal model

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - RHEUMATOID-ARTHRITIS

KW - AUTOANTIGENS

KW - IMMUNITY

KW - THERAPY

U2 - 10.1186/s13550-022-00934-7

DO - 10.1186/s13550-022-00934-7

M3 - Journal article

C2 - 36114433

VL - 12

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

IS - 1

M1 - 62

ER -

ID: 320354288