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Journal of Nuclear Medicine

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Meeting ReportMolecular Targeting Probes - Radioactive & Nonradioactive

SPECT and PET imaging of CD11b-positive immune cells in an orthotopic mouse model of glioma with Zr-89 and Lu-177 labeled Lumi804-anti-CD11b antibody

Shubhanchi Nigam, David Tatum, Alexandra Foster, Elizabeth Plakseychuk, Robert Edinger, Wilson Edwards, Gary Kohanbash, Darren Magda and Carolyn Anderson
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 621;
Shubhanchi Nigam
1University of Pittsburgh Pittsburgh PA United States
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David Tatum
2Lumiphore Berkeley CA United States
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Alexandra Foster
1University of Pittsburgh Pittsburgh PA United States
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Elizabeth Plakseychuk
1University of Pittsburgh Pittsburgh PA United States
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Robert Edinger
1University of Pittsburgh Pittsburgh PA United States
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Wilson Edwards
1University of Pittsburgh Pittsburgh PA United States
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Gary Kohanbash
1University of Pittsburgh Pittsburgh PA United States
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Darren Magda
2Lumiphore Berkeley CA United States
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Carolyn Anderson
1University of Pittsburgh Pittsburgh PA United States
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Abstract

621

Objectives: We recently reported on PET imaging of tumor associated myeloid cells (TAMCs) with 89Zr-labeled anti-CD11b antibody in the orthotopic GL261 mouse model of glioma, where deferrioxamine (DFO) was employed as the chelator (Nigam et al. Mol Imag Biol 2019). The Zr(IV) chelator DFO has disadvantages that include release of Zr-89 in vivo, resulting in bone uptake, as well as lack of utility with radio-lanthanides such as Lu-177. Here we report a novel chelator, Lumi804, that has stability for Zr(IV), as well as several lanthanide (III) ions, including Lu(III), and has been conjugated to the anti-mouse CD11b antibody (clone M1/70; BioLegend) for radiolabeling with Zr-89 and Lu-177. METHODS: Lumi804-Ca-NHS was conjugated to the anti-CD11b antibody. The resulting conjugate, Lumi804-anti-CD11b was purified by SEC. Affinity was determined by gated fluorescence microtiter assays. Lumi804-anti-CD11b was radiolabeled with Zr-89 and Lu-177 and a biodistribution and pre-clinical PET/CT and SPECT/CT was performed.

Results: The binding affinity (Kd) of Eu-Lumi804-anti-CD11b was 2.6 +/- 0.3 nM (n=3), as on J774 macrophages at 4C. Radiolabeling yields of Lumi804-anti-CD11b with Zr-89 and Lu-177 were >96% with molar activities of ~11.8 GBq/μmol. Specific uptake of both 89Zr- and 177Lu-Lumi804-anti-CD11b were observed in the orthotopic GL261 model at 72 h post-injection (Zr-89: 3.4 +/- 0.97 %ID/g right brain with tumor vs 0.31 +/- 0.21 contralateral brain; Lu-177: 5.2 +/- 0.72 %ID/g right brain with tumor vs 0.27 +/- 0.36 contralateral brain). High uptake in the spleen and thymus for both tracers also indicate binding of to CD11b in vivo. A biodistribution comparison of 89Zr-DFO- vs Lumi804-anti-CD11b antibody at 216 hours shows bone uptake of DFO to be 6.3 +/- 2.3 %ID/g vs 0.5 +/- 0.05 %ID/g for Lumi804, suggesting greatly improved in vivo stability of 89Zr-Lumi804-antiCD11b.

Conclusions: These data demonstrate that Lumi804 has superior in vivo stability for Zr-89 compared to DFO and also exhibits versatility for complexing the Ln(III) radiometals that include Lu-177.

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Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
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SPECT and PET imaging of CD11b-positive immune cells in an orthotopic mouse model of glioma with Zr-89 and Lu-177 labeled Lumi804-anti-CD11b antibody
Shubhanchi Nigam, David Tatum, Alexandra Foster, Elizabeth Plakseychuk, Robert Edinger, Wilson Edwards, Gary Kohanbash, Darren Magda, Carolyn Anderson
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 621;

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SPECT and PET imaging of CD11b-positive immune cells in an orthotopic mouse model of glioma with Zr-89 and Lu-177 labeled Lumi804-anti-CD11b antibody
Shubhanchi Nigam, David Tatum, Alexandra Foster, Elizabeth Plakseychuk, Robert Edinger, Wilson Edwards, Gary Kohanbash, Darren Magda, Carolyn Anderson
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 621;
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