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16.09.2019 | Research Article

Preclinical ImmunoPET Imaging of Glioblastoma-Infiltrating Myeloid Cells Using Zirconium-89 Labeled Anti-CD11b Antibody

verfasst von: Shubhanchi Nigam, Lauren McCarl, Rajeev Kumar, Robert S. Edinger, Brenda F. Kurland, Carolyn J. Anderson, Ashok Panigrahy, Gary Kohanbash, W. Barry Edwards

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2020

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Abstract

Purpose

Glioblastoma is a lethal brain tumor, heavily infiltrated by tumor-associated myeloid cells (TAMCs). TAMCs are emerging as a promising therapeutic target as they suppress anti-tumor immune responses and promote tumor cell growth. Quantifying TAMCs using non-invasive immunoPET could facilitate patient stratification for TAMC-targeted treatments and monitoring of treatment efficacy. As TAMCs uniformly express the cell surface marker, integrin CD11b, we evaluated a Zr-89 labeled anti-CD11b antibody for non-invasive imaging of TAMCs in a syngeneic orthotopic mouse glioma model.

Procedures

A human/mouse cross-reactive anti-CD11b antibody (clone M1/70) was conjugated to a DFO chelator and radiolabeled with Zr-89. PET/CT and biodistribution with or without a blocking dose of anti-CD11b Ab were performed 72 h post-injection (p.i.) of [⁸⁹Zr]anti-CD11b Ab in mice bearing established orthotopic syngeneic GL261 gliomas and in non tumor-bearing mice. Flow cytometry and immunohistochemistry of dissected GL261 tumors were conducted to confirm the presence of CD11b⁺ TAMCs.

Results

Significant uptake of [⁸⁹Zr]anti-CD11b Ab was detected at the tumor site (SUVmean = 2.60 ± 0.24) compared with the contralateral hemisphere (SUVmean = 0.6 ± 0.11). Blocking with a 10-fold lower specific activity of [⁸⁹Zr]anti-CD11b Ab markedly reduced the SUV in the right brain (SUVmean = 0.11 ± 0.06), demonstrating specificity. Spleen and lymph nodes (myeloid cell rich organs) also showed high uptake of the tracer, and biodistribution analysis correlated with the imaging results. CD11b expression within the tumor was validated using flow cytometry and immunohistochemistry, which showed high CD11b expression primarily in the tumoral hemisphere compared with the contralateral hemisphere with very minimal accumulation in non tumor-bearing brain.

Conclusion

These data establish that [⁸⁹Zr]anti-CD11b Ab immunoPET targets CD11b⁺ cells (TAMCs) with high specificity in a mouse model of GBM, demonstrating the potential for non-invasive quantification of tumor-infiltrating CD11b⁺ immune cells during disease progression and immunotherapy in patients with GBM.

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Titel: Preclinical ImmunoPET Imaging of Glioblastoma-Infiltrating Myeloid Cells Using Zirconium-89 Labeled Anti-CD11b Antibody
verfasst von: Shubhanchi Nigam
Lauren McCarl
Rajeev Kumar
Robert S. Edinger
Brenda F. Kurland
Carolyn J. Anderson
Ashok Panigrahy
Gary Kohanbash
W. Barry Edwards
Publikationsdatum: 16.09.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01427-1

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Preclinical ImmunoPET Imaging of Glioblastoma-Infiltrating Myeloid Cells Using Zirconium-89 Labeled Anti-CD11b Antibody