18 F-labeled anti-human CD20 cys-diabody for same-day immunoPET in a model of aggressive B cell lymphoma in human CD20 transgenic mice.

Autor: Zettlitz KA; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. kzettlitz@coh.org.; Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, 1500 E Duarte Rd, Duarte, CA, 91010, USA. kzettlitz@coh.org., Tavaré R; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA., Tsai WK; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Yamada RE; Division of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Ha NS; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Bioengineering, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Collins J; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA., van Dam RM; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Bioengineering, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Timmerman JM; Division of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Wu AM; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2019 Feb; Vol. 46 (2), pp. 489-500. Date of Electronic Publication: 2018 Nov 19.
DOI: 10.1007/s00259-018-4214-x
Abstrakt: Purpose: Metabolic imaging using [ 18 F]FDG is the current standard for clinical PET; however, some malignancies (e.g., indolent lymphomas) show low avidity for FDG. The majority of B cell lymphomas express CD20, making it a valuable target both for antibody-based therapy and imaging. We previously developed PET tracers based on the humanised anti-CD20 antibody obinutuzumab (GA101). Preclinical studies showed that the smallest bivalent fragment, the cys-diabody (GAcDb, 54.5 kDa) with a peak uptake at 1-2 h post-injection and a biological half-life of 2-5 h, is compatible with short-lived positron emitters such as fluorine-18 ( 18 F, t 1/2 110 min), enabling same-day imaging.
Methods: GAcDb was radiolabeled using amine-reactive N-succinimidyl 4-[ 18 F]-fluorobenzoate ([ 18 F]SFB), or thiol-reactive N-[2-(4-[ 18 F]-fluorobenzamido)ethyl]maleimide ([ 18 F]FBEM) for site-specific conjugation to C-terminal cysteine residues. Both tracers were used for immunoPET imaging of the B cell compartment in human CD20 transgenic mice (hCD20TM). [ 18 F]FB-GAcDb immunoPET was further evaluated in a disseminated lymphoma (A20-hCD20) syngeneic for hCD20TM and compared to [ 18 F]FDG PET. Tracer uptake was confirmed by ex vivo biodistribution.
Results: The GAcDb was successfully 18 F-radiolabeled using two different conjugation methods resulting in similar specific activities and without impairing immunoreactivity. Both tracers ([ 18 F]FB-GAcDb and [ 18 F]FBEM-GAcDb) specifically target human CD20-expressing B cells in transgenic mice. Fast blood clearance results in high contrast PET images as early as 1 h post injection enabling same-day imaging. [ 18 F]FB-GAcDb immunoPET detects disseminated lymphoma disease in the context of normal tissue expression of hCD20, with comparable sensitivity as [ 18 F]FDG PET but with added specificity for the therapeutic target.
Conclusions: [ 18 F]FB-GAcDb and [ 18 F]FBEM-GAcDb could monitor normal B cells and B cell malignancies non-invasively and quantitatively in vivo. In contrast to [ 18 F]FDG PET, immunoPET provides not only information about the extent of disease but also about presence and localisation of the therapeutic target.
Databáze: MEDLINE
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