In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages

S.Y. Terry, Otto C. Boerman, Danny Gerrits, G.M. Franssen, Josbert Maarten Metselaar, S. Lehmann, Wim J.G. Oyen, C.A. Gerdes, K. Abiraj

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Abstract

Purpose Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. Methods The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with 111In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with 111In-anti-F4/80-A3-1 and isotype-matched control antibody 111In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. Results In vitro binding assays showed that 111In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg 111In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg 111In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced 111In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of 111In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of 111In-rat IgG2b was lower in the spleen, liver and femur when compared to 111In-anti-F4/80-A3-1. Conclusion Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.
Original languageEnglish
Pages (from-to)1430-1438
JournalEuropean journal of nuclear medicine and molecular imaging
Volume42
Issue number9
DOIs
Publication statusPublished - 2015

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Macrophages
Antibodies
Clodronic Acid
Injections
Spleen
Liver
Femur
Inhibitory Concentration 50
Neoplasms
SCID Mice
Single-Photon Emission-Computed Tomography
Heterografts
Antigens
Acids

Keywords

  • IR-99922
  • METIS-315193

Cite this

Terry, S. Y., Boerman, O. C., Gerrits, D., Franssen, G. M., Metselaar, J. M., Lehmann, S., ... Abiraj, K. (2015). In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages. European journal of nuclear medicine and molecular imaging, 42(9), 1430-1438. https://doi.org/10.1007/s00259-015-3084-8
Terry, S.Y. ; Boerman, Otto C. ; Gerrits, Danny ; Franssen, G.M. ; Metselaar, Josbert Maarten ; Lehmann, S. ; Oyen, Wim J.G. ; Gerdes, C.A. ; Abiraj, K. / In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages. In: European journal of nuclear medicine and molecular imaging. 2015 ; Vol. 42, No. 9. pp. 1430-1438.
@article{df04b84348224a45a7bd18a9af91068c,
title = "In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages",
abstract = "Purpose Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. Methods The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with 111In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with 111In-anti-F4/80-A3-1 and isotype-matched control antibody 111In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. Results In vitro binding assays showed that 111In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 {\%} and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg 111In-anti-F4/80-A3-1 resulted in splenic uptake of 78 {\%}ID/g and 31 {\%}ID/g, respectively, and tumour uptake of 1.38 {\%}ID/g and 4.08 {\%}ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg 111In-anti-F4/80-A3-1 from 248 {\%}ID/g to 114 {\%}ID/g and reduced 111In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of 111In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of 111In-rat IgG2b was lower in the spleen, liver and femur when compared to 111In-anti-F4/80-A3-1. Conclusion Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.",
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author = "S.Y. Terry and Boerman, {Otto C.} and Danny Gerrits and G.M. Franssen and Metselaar, {Josbert Maarten} and S. Lehmann and Oyen, {Wim J.G.} and C.A. Gerdes and K. Abiraj",
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year = "2015",
doi = "10.1007/s00259-015-3084-8",
language = "English",
volume = "42",
pages = "1430--1438",
journal = "European journal of nuclear medicine and molecular imaging",
issn = "1619-7070",
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}

Terry, SY, Boerman, OC, Gerrits, D, Franssen, GM, Metselaar, JM, Lehmann, S, Oyen, WJG, Gerdes, CA & Abiraj, K 2015, 'In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages' European journal of nuclear medicine and molecular imaging, vol. 42, no. 9, pp. 1430-1438. https://doi.org/10.1007/s00259-015-3084-8

In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages. / Terry, S.Y.; Boerman, Otto C.; Gerrits, Danny; Franssen, G.M.; Metselaar, Josbert Maarten; Lehmann, S.; Oyen, Wim J.G.; Gerdes, C.A.; Abiraj, K.

In: European journal of nuclear medicine and molecular imaging, Vol. 42, No. 9, 2015, p. 1430-1438.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages

AU - Terry, S.Y.

AU - Boerman, Otto C.

AU - Gerrits, Danny

AU - Franssen, G.M.

AU - Metselaar, Josbert Maarten

AU - Lehmann, S.

AU - Oyen, Wim J.G.

AU - Gerdes, C.A.

AU - Abiraj, K.

N1 - Open access

PY - 2015

Y1 - 2015

N2 - Purpose Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. Methods The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with 111In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with 111In-anti-F4/80-A3-1 and isotype-matched control antibody 111In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. Results In vitro binding assays showed that 111In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg 111In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg 111In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced 111In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of 111In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of 111In-rat IgG2b was lower in the spleen, liver and femur when compared to 111In-anti-F4/80-A3-1. Conclusion Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.

AB - Purpose Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. Methods The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with 111In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with 111In-anti-F4/80-A3-1 and isotype-matched control antibody 111In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. Results In vitro binding assays showed that 111In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg 111In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg 111In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced 111In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of 111In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of 111In-rat IgG2b was lower in the spleen, liver and femur when compared to 111In-anti-F4/80-A3-1. Conclusion Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.

KW - IR-99922

KW - METIS-315193

U2 - 10.1007/s00259-015-3084-8

DO - 10.1007/s00259-015-3084-8

M3 - Article

VL - 42

SP - 1430

EP - 1438

JO - European journal of nuclear medicine and molecular imaging

JF - European journal of nuclear medicine and molecular imaging

SN - 1619-7070

IS - 9

ER -