Publication

Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice

van der Veen, E. L., Suurs, F. V., Cleeren, F., Bormans, G., Elsinga, P. H., Hospers, G. A. P., Lub-de Hooge, M. N., de Vries, E. G. E., de Vries, E. F. J. & F Antunes, I., Sep-2020, In : Journal of Nuclear Medicine. 61, 9, p. 1355-1360 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

van der Veen, E. L., Suurs, F. V., Cleeren, F., Bormans, G., Elsinga, P. H., Hospers, G. A. P., Lub-de Hooge, M. N., de Vries, E. G. E., de Vries, E. F. J., & F Antunes, I. (2020). Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice. Journal of Nuclear Medicine, 61(9), 1355-1360. https://doi.org/10.2967/jnumed.119.238782

Author

van der Veen, Elly L ; Suurs, Frans V ; Cleeren, Frederik ; Bormans, Guy ; Elsinga, Philip H ; Hospers, Geke A P ; Lub-de Hooge, Marjolijn N ; de Vries, Elisabeth G E ; de Vries, Erik F J ; F Antunes, Ines. / Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice. In: Journal of Nuclear Medicine. 2020 ; Vol. 61, No. 9. pp. 1355-1360.

Harvard

van der Veen, EL, Suurs, FV, Cleeren, F, Bormans, G, Elsinga, PH, Hospers, GAP, Lub-de Hooge, MN, de Vries, EGE, de Vries, EFJ & F Antunes, I 2020, 'Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice', Journal of Nuclear Medicine, vol. 61, no. 9, pp. 1355-1360. https://doi.org/10.2967/jnumed.119.238782

Standard

Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice. / van der Veen, Elly L; Suurs, Frans V; Cleeren, Frederik; Bormans, Guy; Elsinga, Philip H; Hospers, Geke A P; Lub-de Hooge, Marjolijn N; de Vries, Elisabeth G E; de Vries, Erik F J; F Antunes, Ines.

In: Journal of Nuclear Medicine, Vol. 61, No. 9, 09.2020, p. 1355-1360.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van der Veen EL, Suurs FV, Cleeren F, Bormans G, Elsinga PH, Hospers GAP et al. Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice. Journal of Nuclear Medicine. 2020 Sep;61(9):1355-1360. https://doi.org/10.2967/jnumed.119.238782


BibTeX

@article{2a3d115ff3ba4abbb10bec46ac08dbcb,
title = "Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice",
abstract = "Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as a PET tracer for T cell imaging. However, production is complex and time-consuming. Therefore, we developed 2 radiolabeled IL2 variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL2 (68Ga-Ga-NODAGA-IL2), and compared their in vitro and in vivo characteristics with 18F-FB-IL2. Methods: Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized, and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60, and 90 min after tracer injection. In vivo binding characteristics were studied in severe combined immunodeficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMC inoculation, and a 60-min dynamic PET scan was acquired, followed by ex vivo biodistribution studies. Specific uptake was determined by coinjection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results:68Ga-Ga-NODAGA-IL2 and 18F-AlF-RESCA-IL2 were produced with radiochemical purity of more than 95% and radiochemical yield of 13.1% ± 4.7% and 2.4% ± 1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with more than 90% being intact tracer after 1 h. In vitro, both tracers displayed preferential binding to activated hPBMCs. Ex vivo biodistribution studies on BALB/c mice showed higher uptake of 18F-AlF-RESCA-IL2 than of 18F-FB-IL2 in liver, kidney, spleen, bone, and bone marrow. 68Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than 18F-FB-IL2 uptake. In vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 and in the Matrigel control group. In addition, 18F-AlF-RESCA-IL2 yielded the highest-contrast PET images of target lymph nodes. Conclusion: Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than that of 18F-FB-IL2. Both tracers showed good in vitro and in vivo characteristics, with high uptake in lymphoid tissue and hPBMC xenografts.",
author = "{van der Veen}, {Elly L} and Suurs, {Frans V} and Frederik Cleeren and Guy Bormans and Elsinga, {Philip H} and Hospers, {Geke A P} and {Lub-de Hooge}, {Marjolijn N} and {de Vries}, {Elisabeth G E} and {de Vries}, {Erik F J} and {F Antunes}, Ines",
note = "Copyright {\textcopyright} 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2020",
month = sep,
doi = "10.2967/jnumed.119.238782",
language = "English",
volume = "61",
pages = "1355--1360",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "SOC NUCLEAR MEDICINE INC",
number = "9",

}

RIS

TY - JOUR

T1 - Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice

AU - van der Veen, Elly L

AU - Suurs, Frans V

AU - Cleeren, Frederik

AU - Bormans, Guy

AU - Elsinga, Philip H

AU - Hospers, Geke A P

AU - Lub-de Hooge, Marjolijn N

AU - de Vries, Elisabeth G E

AU - de Vries, Erik F J

AU - F Antunes, Ines

N1 - Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2020/9

Y1 - 2020/9

N2 - Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as a PET tracer for T cell imaging. However, production is complex and time-consuming. Therefore, we developed 2 radiolabeled IL2 variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL2 (68Ga-Ga-NODAGA-IL2), and compared their in vitro and in vivo characteristics with 18F-FB-IL2. Methods: Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized, and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60, and 90 min after tracer injection. In vivo binding characteristics were studied in severe combined immunodeficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMC inoculation, and a 60-min dynamic PET scan was acquired, followed by ex vivo biodistribution studies. Specific uptake was determined by coinjection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results:68Ga-Ga-NODAGA-IL2 and 18F-AlF-RESCA-IL2 were produced with radiochemical purity of more than 95% and radiochemical yield of 13.1% ± 4.7% and 2.4% ± 1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with more than 90% being intact tracer after 1 h. In vitro, both tracers displayed preferential binding to activated hPBMCs. Ex vivo biodistribution studies on BALB/c mice showed higher uptake of 18F-AlF-RESCA-IL2 than of 18F-FB-IL2 in liver, kidney, spleen, bone, and bone marrow. 68Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than 18F-FB-IL2 uptake. In vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 and in the Matrigel control group. In addition, 18F-AlF-RESCA-IL2 yielded the highest-contrast PET images of target lymph nodes. Conclusion: Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than that of 18F-FB-IL2. Both tracers showed good in vitro and in vivo characteristics, with high uptake in lymphoid tissue and hPBMC xenografts.

AB - Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as a PET tracer for T cell imaging. However, production is complex and time-consuming. Therefore, we developed 2 radiolabeled IL2 variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL2 (68Ga-Ga-NODAGA-IL2), and compared their in vitro and in vivo characteristics with 18F-FB-IL2. Methods: Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized, and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60, and 90 min after tracer injection. In vivo binding characteristics were studied in severe combined immunodeficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMC inoculation, and a 60-min dynamic PET scan was acquired, followed by ex vivo biodistribution studies. Specific uptake was determined by coinjection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results:68Ga-Ga-NODAGA-IL2 and 18F-AlF-RESCA-IL2 were produced with radiochemical purity of more than 95% and radiochemical yield of 13.1% ± 4.7% and 2.4% ± 1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with more than 90% being intact tracer after 1 h. In vitro, both tracers displayed preferential binding to activated hPBMCs. Ex vivo biodistribution studies on BALB/c mice showed higher uptake of 18F-AlF-RESCA-IL2 than of 18F-FB-IL2 in liver, kidney, spleen, bone, and bone marrow. 68Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than 18F-FB-IL2 uptake. In vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 and in the Matrigel control group. In addition, 18F-AlF-RESCA-IL2 yielded the highest-contrast PET images of target lymph nodes. Conclusion: Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than that of 18F-FB-IL2. Both tracers showed good in vitro and in vivo characteristics, with high uptake in lymphoid tissue and hPBMC xenografts.

U2 - 10.2967/jnumed.119.238782

DO - 10.2967/jnumed.119.238782

M3 - Article

C2 - 32111688

VL - 61

SP - 1355

EP - 1360

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 9

ER -

ID: 119042501