Research Article In Vivo Evaluation of Gallium-68-Labeled IRDye800CW as a Necrosis Avid Contrast Agent in Solid Tumors Marcus C.M. Stroet , 1,2 Erik de Blois , 1 Joost Haeck , 3 Yann Seimbille , 1,4 Laura Mezzanotte , 1,2 Marion de Jong , 1 ClemensW.G.M.L¨ owik , 1,2,5 and Kranthi M. Panth 1,2 1 Erasmus MC, University Medical Center Rotterdam, Department of Radiology & Nuclear Medicine, Rotterdam, Netherlands 2 Erasmus MC, University Medical Center Rotterdam, Department of Molecular Genetics, Rotterdam, Netherlands 3 AMIE Core Facility, Erasmus MC, Rotterdam, Netherlands 4 Life Sciences Division, TRIUMF, Vancouver, Canada 5 CHUV Department of Oncology, University of Lausanne, Lausanne, Switzerland Correspondence should be addressed to Clemens W.G.M. L¨ owik; c.lowik@erasmusmc.nl and Kranthi M. Panth; k.panth@ erasmusmc.nl Received 15 October 2021; Revised 17 November 2021; Accepted 18 November 2021; Published 13 December 2021 Academic Editor: Guillermina Ferro Flores Copyright © 2021 Marcus C.M. Stroet et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, is an important biomarker. Tumor necrosis occurs in most solid tumors due to improperly functioning blood vessels that cannot keep up with the rapid growth, especially in aggressively growing tumors. e amount of necrosis per tumor volume is often correlated to rapid tumor proliferation and can be used as a diagnostic tool. Furthermore, efficient therapy against solid tumors will directly or indirectly lead to necrotic tumor cells, and detection of increased tumor necrosis can be an early marker for therapy efficacy. We propose the application of necrosis avid contrast agents to detect therapy-induced tumor necrosis. Herein, we advance gallium-68-labeled IRDye800CW, a near-infrared fluorescent dye that exhibits excellent necrosis avidity, as a potential PETtracer for in vivo imaging of tumor necrosis. We developed a reliable labeling procedure to prepare [ 68 Ga]Ga-DOTA-PEG 4 -IRDye800CW ([ 68 Ga]Ga-1) with a radiochemical purity of >96% (radio-HPLC). e prominent dead cell binding of fluorescence and radioactivity from [ 68 Ga]Ga-1 was confirmed with dead and alive cultured 4T1-Luc2 cells. [ 68 Ga]Ga-1 was injected in 4T1-Luc2 tumor-bearing mice, and specific fluorescence and PET signal were observed in the spontaneously developing tumor necrosis. e ip injection of D-luciferin enabled simultaneous bioluminescence imaging of the viable tumor regions. Tumor necrosis binding was confirmed ex vivo by colocalization of fluorescence uptake with TUNEL dead cell staining and radioactivity uptake in dichotomized tumors and frozen tumor sections. Our presented study shows that [ 68 Ga]Ga-1 is a promising PET tracer for the detection of tumor necrosis. 1.Introduction Excessive occurrence of cell death is a hallmark for severe disease in many pathologies, such as sepsis [1], pancreatitis [2], or acute myocardial infarction [3]. Moreover, most solid tumors develop necrotic tissue due to the growth rate of the tumor mass surpassing the rate of vascularization. As a result, tumor necrosis is often associated with aggressive tumor types and poor disease prognosis [4, 5]. Currently, noninvasive techniques for necrosis detection are lacking in the clinic. ere have been several agents reaching clinical trials targeting apoptosis markers, for instance, radiolabeled Annexin V, which targets exposed phosphoserines [6], or [ 18 F]ICMT-11 targeting caspase-3/7 activation [7, 8]. However, due to the lack of specificity, these tracers have so far failed to reach the clinic [9–11]. Hindawi Contrast Media & Molecular Imaging Volume 2021, Article ID 2853522, 8 pages https://doi.org/10.1155/2021/2853522