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• W2887444888 abstract "// Emilie M.J. van Brummelen 1, 6 , Marc C. Huisman 2 , Linda J. de Wit-van der Veen 1 , Tapan K. Nayak 3 , Marcel P.M. Stokkel 1 , Emma R. Mulder 2 , Otto S. Hoekstra 2 , Danielle J. Vugts 2 , Guus A.M.S. Van Dongen 2 , Henk M. Verheul 2 , Stefan Evers 4 , Jean J. L. Tessier 3 , Jose Saro 4 , Jan H.M. Schellens 1, 5 and C. Willemien Menke-van der Houven van Oordt 2 1 The Netherlands Cancer Institute, Amsterdam, The Netherlands 2 VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands 3 Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland 4 Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland 5 Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands 6 Centre for Human Drug Research, Leiden, The Netherlands Correspondence to: C. Willemien Menke-van der Houven van Oordt, email: c.menke@vumc.nl Keywords: immunocytokine; interleukin-2; 89 Zr; biodistribution; immuno-PET Received: March 24, 2018      Accepted: April 21, 2018      Published: May 15, 2018 ABSTRACT Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) α binding. We describe the biodistribution and tumor accumulation of 89 Zr-labeled CEA-IL2v. Twenty-four patients with advanced solid CEA positive (CEA+) or negative (CEA−) tumors received CEA-IL2v 6 mg (4 CEA+; 3 CEA−), 20 mg (9 CEA+), or 30 mg (4 CEA+; 4 CEA−) biweekly. In cycle 1, 2 mg of the total dose comprised 89 Zr-CEA-IL2v (50 MBq) and serial 89 Zr-PET imaging was conducted. Four CEA+ patients with visually confirmed 89 Zr-CEA-IL2v tumor accumulation at 20 mg had repeated 89 Zr-PET imaging during cycle 4. 89 Zr-CEA-IL2v immuno-PET demonstrated preferential drug accumulation in CEA+ tumors (%ID/mL peak CEA− 3.6 × 10 −3 vs. CEA+ 6.7 ×∙10 −3 ). There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses ≥20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding. Reduced exposure and reduced tumor accumulation (%ID/mL peak 57% lower) on cycle 4 vs. cycle 1 was consistent with peripheral expansion of immune cells. The findings of this immune PET imaging study with 89 Zr-CEA-IL2v support the therapeutic concept of CEA-IL2v, confirming selective and targeted tumor accumulation with this novel immunocytokine." @default.
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• W2887444888 date "2018-05-15" @default.
• W2887444888 modified "2023-10-11" @default.
• W2887444888 title "89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding" @default.
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• W2887444888 doi "https://doi.org/10.18632/oncotarget.25343" @default.
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