{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:14:54Z","timestamp":1768724094923,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A phage\u2010derived human monoclonal antibody against VEGF\u2010C was developed as a potential anti\u2010tumor therapeutic and exhibited fast clearance in preclinical species, with notably faster clearance in serum than in plasma. The purpose of this work was to understand the factors contributing to its fast clearance. In vitro incubations in animal and human blood, plasma, and serum were conducted with radiolabeled anti\u2010VEGF\u2010C to determine potential protein and cell\u2010based interactions with the antibody as well as any matrix\u2010dependent recovery dependent upon the matrix. A tissue distribution study was conducted in mice with and without heparin infusion in order to identify a tissue sink and determine whether heparin could affect antibody recovery from serum and\/or plasma. Incubation of radiolabeled anti\u2010VEGF\u2010C in human and animal blood, plasma, or serum revealed that the antibody formed a complex with an endogenous protein, likely VEGF\u2010C. This complex was trapped within the blood clot during serum preparation from blood, but not within the blood cell pellet during plasma preparation. Low level heparin infusion in mice slowed down clot formation during serum preparation and allowed for better recovery of the radiolabeled antibody in serum. No tissue sink was found in mice. Thus, during this characterization, we determined that the blood sampling matrix greatly impacted the amount of antibody recovered in the samples, therefore, altering its derived pharmacokinetic parameters. Target biology should be considered when selecting appropriate sampling matrices for PK analysis.<\/jats:p>","DOI":"10.1002\/prp2.573","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T18:56:52Z","timestamp":1583261812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Complex formation of anti\u2010VEGF\u2010C with VEGF\u2010C released during blood coagulation resulted in an artifact in its serum pharmacokinetics"],"prefix":"10.1002","volume":"8","author":[{"given":"Daniela","family":"Bumbaca Yadav","sequence":"first","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Arthur E.","family":"Reyes","sequence":"additional","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Gupta","sequence":"additional","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Michel","family":"Vernes","sequence":"additional","affiliation":[{"name":"Biochemical and Cellular Pharmacology Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y. Gloria","family":"Meng","sequence":"additional","affiliation":[{"name":"Biochemical and Cellular Pharmacology Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle G.","family":"Schweiger","sequence":"additional","affiliation":[{"name":"Safety Assessment Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon L.","family":"Stainton","sequence":"additional","affiliation":[{"name":"Safety Assessment Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germaine","family":"Fuh","sequence":"additional","affiliation":[{"name":"Antibody Engineering Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Fielder","sequence":"additional","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrita V.","family":"Kamath","sequence":"additional","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8214-6825","authenticated-orcid":false,"given":"Ben\u2010Quan","family":"Shen","sequence":"additional","affiliation":[{"name":"Preclinical and Translational Pharmacokinetics and Pharmacodynamics Department Genentech, Inc. South San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2007.01.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(01)00027-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.13.3898"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.01.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2006.4.73"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0885"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.4.672"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.22189"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.4049\/jimmunol.147.5.1548","article-title":"IL\u201012: Monocloncal antibodies specific for the 40\u2010kDa subunit block receptor binding and biological activity on activated human lymphoblasts","volume":"147","author":"Chizzonite R","year":"1991","journal-title":"J Immunol"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1958.12.3.453"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421779112"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/62.4.545"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.036533"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055309"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2011.0276"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615158"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2001.02476.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12007"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2006.10.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-9560-4-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(01)00420-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02762-6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.6.2.257"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(93)90049-T"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.3.251"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.573","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:42:49Z","timestamp":1694068969000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,3]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/prp2.573"],"URL":"https:\/\/doi.org\/10.1002\/prp2.573","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,3]]},"assertion":[{"value":"2019-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00573"}}