Choyke, Peter L.

Abstract Techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. However, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achieving long-term expression of reporter genes compatible with safe noninvasive imaging. In this study, the rhesus sodium/iodide symporter (NIS) gene was incorporated into rhesus macaque induced pluripotent stem cells (RhiPSCs) via CRISPR/Cas9. Cardiomyocytes derived from NIS-RhiPSCs (NIS-RhiPSC-CMs) exhibited overall similar morphological and electrophysiological characteristics compared to parental control RhiPSC-CMs at baseline and with exposure to physiological levels of sodium iodide. Mice were injected intramyocardially with 2 million NIS-RhiPSC-CMs immediately following myocardial infarction, and serial positron emission tomography/computed tomography was performed with 18F-tetrafluoroborate to monitor transplanted cells in vivo. NIS-RhiPSC-CMs could be detected until study conclusion at 8 to 10 weeks postinjection. This NIS-based molecular imaging platform, with optimal safety and sensitivity characteristics, is primed for translation into large-animal preclinical models and clinical trials.

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.