{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:14:11Z","timestamp":1792026851740,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["5P50CA058236"],"award-info":[{"award-number":["5P50CA058236"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["P30CA006973"],"award-info":[{"award-number":["P30CA006973"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Current preclinical models of metastatic prostate cancer (PCa) require sophisticated technologies and\/or genetically engineered cells for the noninvasive monitoring of tumors in remote sites, such as bone. Recent developments in circulating tumor DNA (ctDNA) analysis provide an alternative method for noninvasive tumor monitoring at a low cost. Here, we sought to evaluate human Alu and LINE\u20101 ctDNA for the longitudinal measurement of subcutaneous and intratibial human PCa xenograft growth and response to ionizing radiation (IR) through comparison with standard slide caliper and bioluminescence measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Intratibial and subcutaneous xenografts were established in male athymic nude mice using LNCaP cells that stably express firefly luciferase. A subset of tumors was treated with a single dose of IR (CT\u2010guided focal IR, 6\u2009Gy). Tumor measurements were simultaneously taken by slide caliper (subcutaneous only), in vivo bioluminescence imaging, and quantitative real\u2010time PCR (qPCR) of human\u2010specific Alu and LINE\u20101 ctDNA for several weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of ctDNA and bioluminescence increased concordantly with subcutaneous and intratibial tumor growth. A statistically significant correlation (Spearman) was observed between ctDNA and subcutaneous tumor volume (LINE\u20101, <jats:italic>r<\/jats:italic>\u2009=\u2009.94 and Alu, <jats:italic>r<\/jats:italic>\u2009=\u2009.95, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001), ctDNA and bioluminescence (LINE\u20101, <jats:italic>r<\/jats:italic>\u2009=\u2009.66 and Alu, <jats:italic>r<\/jats:italic>\u2009=\u2009.60, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.002), and bioluminescence and tumor volume (<jats:italic>r<\/jats:italic>\u2009=\u2009.66, <jats:italic>p<\/jats:italic>\u2009=\u2009.0003). Bioluminescence and ctDNA were also significantly correlated in intratibial tumors (LINE\u20101, <jats:italic>r<\/jats:italic>\u2009=\u2009.82 and Alu, <jats:italic>r<\/jats:italic>\u2009=\u2009.81, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Following external beam IR, the tumor responses varied briefly by method of measurement, but followed a similar trend. Statistically significant correlations were maintained between ctDNA and slide caliper measurement in irradiated subcutaneous tumors (LINE\u20101, <jats:italic>r<\/jats:italic>\u2009=\u2009.64 and Alu, <jats:italic>r<\/jats:italic>\u2009=\u2009.44, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.02), and ctDNA and bioluminescence in intratibial tumors (LINE\u20101, <jats:italic>r<\/jats:italic>\u2009=\u2009.55, <jats:italic>p<\/jats:italic>\u2009=\u2009.018).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Real\u2010time qPCR of circulating human Alu and LINE\u20101 DNA provides an accurate measurement of subcutaneous and intratibial xenograft burden that is comparable with conventional bioluminescence imaging and slide caliper measurement. Transient differences in measurements were observed following tumor\u2010targeted IR, but overall all measurements mirrored tumor growth and response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24171","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T12:05:54Z","timestamp":1621944354000},"page":"745-753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Longitudinal measurement of subcutaneous and intratibial human prostate cancer xenograft growth and response to ionizing radiation by plasma Alu and LINE\u20101 ctDNA: A comparison to standard methods"],"prefix":"10.1002","volume":"81","author":[{"given":"Alok","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Zennami","sequence":"additional","affiliation":[{"name":"Department of Urology, The James Buchanan Brady Urologic Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Velarde","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-1239","authenticated-orcid":false,"given":"Daniel L. J.","family":"Thorek","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Radiology and Biomedical Engineering Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasan","family":"Yegnasubramanian","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore L.","family":"DeWeese","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Urology, The James Buchanan Brady Urologic Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5449-0362","authenticated-orcid":false,"given":"Shawn E.","family":"Lupold","sequence":"additional","affiliation":[{"name":"Department of Urology, The James Buchanan Brady Urologic Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0605"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/hp.2000.6698"},{"issue":"3","key":"e_1_2_10_6_1","first-page":"1038","article-title":"Rapid (\"warm\") autopsy study for procurement of metastatic prostate cancer","volume":"6","author":"Rubin MA","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0931"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.07.020"},{"issue":"17","key":"e_1_2_10_9_1","first-page":"4453","article-title":"Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone","volume":"59","author":"Jacob K","year":"1999","journal-title":"Cancer Res"},{"issue":"6","key":"e_1_2_10_10_1","first-page":"1832","article-title":"Use of the stromal cell\u2010derived factor\u20101\/CXCR4 pathway in prostate cancer metastasis to bone","volume":"62","author":"Taichman RS","year":"2002","journal-title":"Cancer 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