Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Morris, Zachary S.; Weichert, Jamey P.; Saker, Jarob; Armstrong, Eric A.; Besemer, Abigail; Bednarz, Bryan; Kimple, Randall J.; Harari, Paul M.
• Is Part Of: Radiotherapy and oncology. Volume 116:Issue 3(2015:Sep.)
• Page Start: 504
• Page End: 509
• Publication Date: 2015-09
• Subjects: Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2015.06.015
• Languages: English
• ISSNs: 0167-8140

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background and purpose</title> <p id="sp0005">CLR1404 is a phospholipid ether that exhibits selective uptake and retention in malignant tissues. Radiolabeled CLR1404 enables tumor-specific positron-emission tomography (PET) imaging (<sup>124</sup>I) and targeted delivery of ionizing radiation (<sup>131</sup>I). Here we describe the first preclinical studies of this diapeutic molecule in head and neck cancer (HNC) models.</p> </sec> <sec> <title id="st015">Material and methods</title> <p id="sp0010">Tumor-selective distribution of <sup>124</sup>I-CLR1404 and therapeutic efficacy of <sup>131</sup>I-CLR1404 were tested in HNC cell lines and patient-derived xenograft tumor models. Monte Carlo dose calculations and <sup>124</sup>I-CLR1404 PET/CT imaging were used to examine <sup>131</sup>I-CLR1404 dosimetry in preclinical HNC tumor models.</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">HNC tumor xenograft studies including patient-derived xenografts demonstrate tumor-selective uptake and retention of <sup>124</sup>I-CLR1404 resulting in a model of highly conformal dose distribution for <sup>131</sup>I-CLR1404. We observe dose-dependent response to <sup>131</sup>I-CLR1404 with respect to HNC tumor xenograft growth inhibition and this effect is maintained together with external beam radiation.</p> </sec> <sec> <title id="st025">Conclusions</title> <p id="sp0020">We confirm the utility of CLR1404 for tumor imaging and treatment of HNC. This promising agent warrants further investigation in a developing phase I trial combining <sup>131</sup>I-CLR1404 with reduced-dose external beam radiation in patients with loco-regionally recurrent HNC.</p> </sec> </abstract>