{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:37:56Z","timestamp":1790213876154,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Contrast Media &amp; Molecular Imaging"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p>We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431\/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of <jats:sup>89<\/jats:sup>Zr-B3 were dose-independent when 3 doses, 2, 15, and 60\u2009<jats:italic>\u03bc<\/jats:italic>g B3, were compared at 24\u2009h after injection. In contrast, tumor and organ uptakes of <jats:sup>89<\/jats:sup>Zr-amatuximab were dose-dependent, whereby a high dose (60\u2009<jats:italic>\u03bc<\/jats:italic>g) was needed to achieve tumor targeting comparable to the low dose (2\u2009<jats:italic>\u03bc<\/jats:italic>g) of <jats:sup>89<\/jats:sup>Zr-B3, suggesting that shed mesothelin may affect amatuximab tumor targeting as well as serum half-life. The autoradiography analysis showed that the distribution of <jats:sup>89<\/jats:sup>Zr-B3 was nonuniform with the radioactivity primarily localized at the tumor periphery independent of the B3 dose. However, the autoradiography analysis for <jats:sup>89<\/jats:sup>Zr-amatuximab showed dose-dependent distribution profiles of the radiolabel; at 10\u2009<jats:italic>\u03bc<\/jats:italic>g dose, the radiolabel penetrated toward the tumor core with its activity comparable to that at the tumor periphery, whereas at 60\u2009<jats:italic>\u03bc<\/jats:italic>g dose, the distribution profile became similar to those of <jats:sup>89<\/jats:sup>Zr-B3. These results suggest that shed antigen in blood may act as a decoy requiring higher doses of mAb to improve serum half-life as well as tumor targeting. Systemic mAb concentration should be at a severalfold molar excess to the shed Ag in blood to overcome the hepatic processing of mAb-Ag complexes. On the other hand, mAb concentration should remain lower than the shed Ag concentration in the tumor ECS to maximize tumor penetration by passing binding site barriers.<\/jats:p>","DOI":"10.1155\/2018\/2461257","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T19:30:48Z","timestamp":1520883048000},"page":"1-12","source":"Crossref","is-referenced-by-count":12,"title":["Tumor-Shed Antigen Affects Antibody Tumor Targeting: Comparison of Two <sup>89<\/sup>Zr-Labeled Antibodies Directed against Shed or Nonshed Antigens"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-9560","authenticated-orcid":true,"given":"Jae-Ho","family":"Lee","sequence":"first","affiliation":[{"name":"Radiopharmaceutical Laboratory, Nuclear Medicine, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-3840","authenticated-orcid":true,"given":"Heejung","family":"Kim","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Laboratory, Nuclear Medicine, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Laboratory, Nuclear Medicine, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence P.","family":"Szajek","sequence":"additional","affiliation":[{"name":"Positron Emission Tomography Department, Clinical Center, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Grasso","sequence":"additional","affiliation":[{"name":"Morphotek, Inc., Exton, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insook","family":"Kim","sequence":"additional","affiliation":[{"name":"Applied\/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9199-4984","authenticated-orcid":true,"given":"Chang H.","family":"Paik","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Laboratory, Nuclear Medicine, Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3236"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12626"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.93"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.163824"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2015.07.008"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2011.05.003"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8051(94)00098-5"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110716"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e31819b7c8e"},{"issue":"12","key":"9","first-page":"2834","volume":"53","year":"1993","journal-title":"Cancer Research"},{"issue":"14","key":"11","first-page":"3781","volume":"51","year":"1991","journal-title":"Cancer Research"},{"issue":"5","key":"12","first-page":"1720","volume":"6","year":"2000","journal-title":"Clinical Cancer Research"},{"issue":"20","key":"13","first-page":"5755","volume":"62","year":"2002","journal-title":"Cancer Research"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008859"},{"issue":"8","key":"15","first-page":"1271","volume":"44","year":"2003","journal-title":"Journal of Nuclear Medicine"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2009.05.007"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.13"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(86)21067-8"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2304"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0336"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2405"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708101104"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.06.025"},{"issue":"15","key":"25","first-page":"4478","volume":"50","year":"1990","journal-title":"Cancer Research"}],"container-title":["Contrast Media &amp; 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