{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:56:05Z","timestamp":1790394965528,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2015,8,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 (<jats:sup>111<\/jats:sup>In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Nineteen patients were enrolled. <jats:sup>111<\/jats:sup>In-CS-1008 uptake in tumor was observed in only 12 patients (63%). <jats:sup>111<\/jats:sup>In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. <jats:sup>111<\/jats:sup>In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti\u2013CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with <jats:sup>111<\/jats:sup>In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor\u20135 expression in archived tumor samples did not correlate with <jats:sup>111<\/jats:sup>In-CS-1008 uptake (P = .5) or tumor response (P = .6). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Death-receptor\u20135 imaging with <jats:sup>111<\/jats:sup>In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2014.60.4256","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T02:55:59Z","timestamp":1435632959000},"page":"2609-2616","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":32,"title":["Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer"],"prefix":"10.1200","volume":"33","author":[{"given":"Marika","family":"Ciprotti","sequence":"first","affiliation":[{"name":"Marika Ciprotti, Niall C. 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