{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:44:46Z","timestamp":1791218686261,"version":"4.1.0"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2015,11,11]],"date-time":"2015-11-11T00:00:00Z","timestamp":1447200000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000015","name":"US Department of Energy","doi-asserted-by":"crossref","award":["DOE-SC0008384"],"award-info":[{"award-number":["DOE-SC0008384"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["125246-RSG-13-099-01-CCE"],"award-info":[{"award-number":["125246-RSG-13-099-01-CCE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007015","name":"the University of Wisconsin - Madison","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIBIB\/NCI 1R01CA169365"],"award-info":[{"award-number":["NIBIB\/NCI 1R01CA169365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIBIB\/NCI P30CA014520"],"award-info":[{"award-number":["NIBIB\/NCI P30CA014520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fulbright Scholar Program","award":["1831\/FNPDR\/2013"],"award-info":[{"award-number":["1831\/FNPDR\/2013"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["W81XWH-11-1-0644"],"award-info":[{"award-number":["W81XWH-11-1-0644"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Scandium-44 (t1\/2 = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with 44Sc for in vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N\u2032,N\u2033,N\u2033-pentaacetic acid (CHX-A\u2033-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after 44Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of \u223c12% ID\/g at 4 h postinjection) of 44Sc\u2013CHX-A\u2033-DTPA\u2013Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. This successful strategy for immunoPET imaging of EGFR expression using 44Sc\u2013CHX-A\u2033-DTPA\u2013Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.<\/jats:p>","DOI":"10.1021\/bc500415x","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T22:51:45Z","timestamp":1415746305000},"page":"2197-2204","source":"Crossref","is-referenced-by-count":93,"title":["Matching the Decay Half-Life with the Biological Half-Life:\nImmunoPET Imaging with 44Sc-Labeled Cetuximab Fab Fragment"],"prefix":"10.1021","volume":"25","author":[{"given":"Rubel","family":"Chakravarty","sequence":"first","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53792"]},{"name":"Bhabha Atomic Research Centre , , ,","place":["Mumbai, India, 400085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Goel","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector F.","family":"Valdovinos","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinier","family":"Hernandez","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Hong","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53792"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Nickles","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibo","family":"Cai","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53792"]},{"name":"University of Wisconsin\u2212Madison , , , ,","place":["Madison, Wisconsin, United States, 53705"]},{"name":"University of Wisconsin Carbone Cancer Center , , ,","place":["Madison, Wisconsin, United States, 53792"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,11,11]]},"reference":[{"key":"2026090400181472400_cit1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/1874471011205030187","article-title":"Scandium-44:\nbenefits of a long-lived PET radionuclide available from the 44Ti\/44Sc generator system","volume":"5","author":"Roesch","year":"2012","journal-title":"Curr. Radiopharm."},{"key":"2026090400181472400_cit2","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.apradiso.2012.04.030","article-title":"Cyclotron\nproduced 44gSc from natural calcium","volume":"70","author":"Severin","year":"2012","journal-title":"Appl. Radiat. Isot."},{"key":"2026090400181472400_cit3","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1021\/cr3003104","article-title":"Radiometals for combined imaging and therapy","volume":"113","author":"Cutler","year":"2013","journal-title":"Chem. Rev."},{"key":"2026090400181472400_cit4","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1016\/j.apradiso.2012.08.004","article-title":"44Sc-DOTA-BN[2\u201314]NH2 in comparison to 68Ga-DOTA-BN[2\u201314]NH2 in pre-clinical investigation.\nIs 44Sc a potential radionuclide for PET?","volume":"70","author":"Koumarianou","year":"2012","journal-title":"Appl. Radiat. Isot."},{"key":"2026090400181472400_cit5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11307-012-0561-3","article-title":"Imaging of protein synthesis: in vitro and in vivo\nevaluation of 44Sc-DOTA-puromycin","volume":"15","author":"Eigner","year":"2013","journal-title":"Mol. Imaging Biol."},{"key":"2026090400181472400_cit6","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.2967\/jnumed.113.123810","article-title":"Promises of cyclotron-produced 44Sc as a diagnostic\nmatch for trivalent beta-emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate","volume":"54","author":"Muller","year":"2013","journal-title":"J. Nucl.\nMed."},{"key":"2026090400181472400_cit7","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1021\/mp500343j","article-title":"44Sc: an\nattractive isotope for peptide-based PET imaging","volume":"11","author":"Hernandez","year":"2014","journal-title":"Mol. Pharmaceutics"},{"key":"2026090400181472400_cit8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jinorgbio.2010.11.003","article-title":"Macrocyclic complexes of scandium radionuclides as\nprecursors for diagnostic and therapeutic radiopharmaceuticals","volume":"105","author":"Majkowska-Pilip","year":"2011","journal-title":"J. Inorg. Biochem"},{"key":"2026090400181472400_cit9","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/med.21299","article-title":"Imaging EGFR and HER2 by PET and SPECT: a review","volume":"34","author":"Corcoran","year":"2014","journal-title":"Med. Res. Rev."},{"key":"2026090400181472400_cit10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1358\/dot.2005.41.2.882662","article-title":"Cetuximab: an epidermal growth factor receptor chemeric\nhuman-murine monoclonal antibody","volume":"41","author":"Harding","year":"2005","journal-title":"Drugs Today"},{"key":"2026090400181472400_cit11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3390\/ph7030311","article-title":"Radiolabeled cetuximab\nconjugates for EGFR targeted\ncancer diagnostics and therapy","volume":"7","author":"Sihver","year":"2014","journal-title":"Pharmaceuticals"},{"key":"2026090400181472400_cit12","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1053\/j.semnuclmed.2009.12.005","article-title":"Antibody vectors\nfor imaging","volume":"40","author":"Olafsen","year":"2010","journal-title":"Semin. Nucl.\nMed."},{"key":"2026090400181472400_cit13","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.copbio.2011.06.007","article-title":"Engineering antibodies and proteins\nfor molecular in vivo imaging","volume":"22","author":"Romer","year":"2011","journal-title":"Curr. Opin. Biotechnol."},{"key":"2026090400181472400_cit14","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/nbt1142","article-title":"Engineered antibody\nfragments and the rise of single\ndomains","volume":"23","author":"Holliger","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"2026090400181472400_cit15","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.radonc.2013.06.034","article-title":"111In-cetuximab-F(ab\u2032)2 SPECT imaging for quantification of accessible epidermal\ngrowth factor receptors (EGFR) in HNSCC xenografts","volume":"108","author":"van Dijk","year":"2013","journal-title":"Radiother. Oncol."},{"key":"2026090400181472400_cit16","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.2967\/jnumed.113.123612","article-title":"Imaging of epidermal growth factor\nreceptor expression in head and neck cancer with SPECT\/CT and 111In-labeled cetuximab-F(ab\u2032)2","volume":"54","author":"van Dijk","year":"2013","journal-title":"J. Nucl. Med."},{"key":"2026090400181472400_cit17","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/btpr.1849","article-title":"Online integrity\nmonitoring in the protein A step of mAb production processes-increasing\nreliability and process robustness","volume":"30","author":"Bork","year":"2014","journal-title":"Biotechnol.\nProg."},{"key":"2026090400181472400_cit18","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1002\/bit.24955","article-title":"A tandem laboratory\nscale protein purification process using Protein A affinity and anion\nexchange chromatography operated in a weak partitioning mode","volume":"110","author":"Shamashkin","year":"2013","journal-title":"Biotechnol. Bioeng."},{"key":"2026090400181472400_cit19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chroma.2013.07.096","article-title":"A safe, effective, and facility compatible cleaning in place procedure\nfor affinity resin in large-scale monoclonal antibody purification","volume":"1308","author":"Wang","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"2026090400181472400_cit20","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jlcr.3140","article-title":"A systematic comparative evaluation\nof 90Y-labeled bifunctional chelators for their use in\ntargeted therapy","volume":"57","author":"Chakravarty","year":"2014","journal-title":"J. Labelled Compd. Radiopharm."},{"key":"2026090400181472400_cit21","first-page":"166","article-title":"Bifunctional\nchelates for metal nuclides","volume":"52","author":"Brechbiel","year":"2008","journal-title":"Q. J. Nucl. Med.\nMol. Imaging"},{"key":"2026090400181472400_cit22","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1007\/s00259-006-0361-6","article-title":"Quantitative PET of EGFR expression\nin xenograft-bearing mice using 64Cu-labeled cetuximab,\na chimeric anti-EGFR monoclonal antibody","volume":"34","author":"Cai","year":"2007","journal-title":"Eur.\nJ. Nucl. Med. Mol. Imaging"},{"key":"2026090400181472400_cit23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijrobp.2003.11.041","article-title":"Review\nof epidermal growth factor receptor biology","volume":"59","author":"Herbst","year":"2004","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"2026090400181472400_cit24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2967\/jnumed.108.054312","article-title":"Disparity between in\nvivo EGFR expression and 89Zr-labeled cetuximab uptake\nassessed with PET","volume":"50","author":"Aerts","year":"2009","journal-title":"J. Nucl. Med."},{"key":"2026090400181472400_cit25","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.apradiso.2010.04.003","article-title":"Post-elution processing\nof 44Ti\/44Sc generator-derived 44Sc for clinical application","volume":"68","author":"Pruszynski","year":"2010","journal-title":"Appl. Radiat.\nIsot."},{"key":"2026090400181472400_cit26","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.nucmedbio.2013.12.016","article-title":"44gSc production using\na water target on a 13 MeV cyclotron","volume":"41","author":"Hoehr","year":"2014","journal-title":"Nucl.\nMed. Biol."},{"key":"2026090400181472400_cit27","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1039\/C3CS60304K","article-title":"Matching chelators\nto radiometals for radiopharmaceuticals","volume":"43","author":"Price","year":"2014","journal-title":"Chem.\nSoc. Rev."},{"key":"2026090400181472400_cit28","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/BF00256915","article-title":"Comparative imaging\nand biodistribution studies with an anti-CEA monoclonal antibody and\nits F(ab)2 and Fab fragments in mice with colon carcinoma\nxenografts","volume":"12","author":"Andrew","year":"1986","journal-title":"Eur. J. Nucl. Med."},{"key":"2026090400181472400_cit29","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1158\/1535-7163.MCT-04-0280","article-title":"Epidermal\ngrowth factor receptor (EGFR)-related protein\ninhibits multiple members of the EGFR family in colon and breast cancer\ncells","volume":"4","author":"Xu","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"2026090400181472400_cit30","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s00259-012-2334-2","article-title":"PET imaging\nof CD105\/endoglin expression with a 61\/64Cu-labeled\nFab antibody fragment","volume":"40","author":"Zhang","year":"2013","journal-title":"Eur. J. Nucl. Med. Mol.\nImaging"},{"key":"2026090400181472400_cit31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.apradiso.2014.09.020","article-title":"Separation\nof cyclotron-produced 44Sc from a natural calcium target\nusing a dipentyl pentylphosphonate functionalized extraction resin","volume":"95","author":"Valdovinos","year":"2014","journal-title":"Appl. Radiat. Isot."}],"container-title":["Bioconjugate Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/bc500415x","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/12\/2197\/7846150\/bc500415x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/12\/2197\/7846150\/bc500415x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:49:32Z","timestamp":1788796172000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bcches\/article\/25\/12\/2197\/770563\/Matching-the-Decay-Half-Life-with-the-Biological"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,11]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,11,11]]},"published-print":{"date-parts":[[2014,12,17]]}},"URL":"https:\/\/doi.org\/10.1021\/bc500415x","relation":{},"ISSN":["1043-1802","1520-4812"],"issn-type":[{"value":"1043-1802","type":"print"},{"value":"1520-4812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,11]]}}}