{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:41:34Z","timestamp":1791024094585,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,6,15]]},"abstract":"<jats:p>\n                    Direct enzyme replacement therapy (ERT) has been introduced as a means to treat a number of rare, complex genetic conditions associated with lysosomal dysfunction. Gaucher disease was the first for which this therapy was applied and remains the prototypical example. Although ERT using recombinant lysosomal enzymes has been shown to be effective in altering the clinical course of Gaucher disease, Fabry disease, Hurler syndrome, Hunter syndrome, Maroteaux-Lamy syndrome, and Pompe disease, the recalcitrance of certain disease manifestations underscores important unanswered questions related to dosing regimes, tissue half-life of the recombinant enzyme and the ability of intravenously administered enzyme to reach critical sites of known disease pathology. We have developed an innovative method for tagging acid \u03b2-glucocerebrosidase (GCase), the recombinant enzyme formulated in Cerezyme\u00ae used to treat Gaucher disease, using an\n                    <jats:sup>18<\/jats:sup>\n                    F-labeled substrate analogue that becomes trapped within the active site of the enzyme. Using micro-PET we show that the tissue distribution of injected enzyme can be imaged in a murine model and that the PET data correlate with tissue\n                    <jats:sup>18<\/jats:sup>\n                    F counts. Further we show that PET imaging readily monitors pharmacokinetic changes effected by receptor blocking. The ability to\n                    <jats:sup>18<\/jats:sup>\n                    F-label GCase to monitor the enzyme distribution and tissue half-life in vivo by PET provides a powerful research tool with an immediate clinical application to Gaucher disease and a clear path for application to other ERTs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1003247107","type":"journal-article","created":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T20:51:16Z","timestamp":1275425476000},"page":"10842-10847","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Imaging of enzyme replacement therapy using PET"],"prefix":"10.1073","volume":"107","author":[{"given":"Christopher P.","family":"Phenix","sequence":"first","affiliation":[{"name":"Tri-University Meson Facility (TRIUMF), 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3;"},{"name":"Departments of Chemistry and Biochemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Rempel","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Colobong","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 W28th Avenue, Vancouver, BC, Canada V5Z 4H4; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris J.","family":"Doudet","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Neurology, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Adam","sequence":"additional","affiliation":[{"name":"Tri-University Meson Facility (TRIUMF), 4004 Wesbrook Mall, Vancouver, BC, Canada V6T 2A3;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne A.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 W28th Avenue, Vancouver, BC, Canada V5Z 4H4; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Withers","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Biochemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767180-00005"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511110200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.11.011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116409"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00156a015"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)78077-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00258a047"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar970172"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.2580311207"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.466"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/00404-0399(50)1031C-"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1139\/v90-288"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/recl.19800991109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00049a035"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00044a034"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00104a060"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50010-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00156a016"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200502662"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(86)90287-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor873"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199602000-00021"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.00344.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.2807.409k08_2807_2816"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2008.163"},{"key":"e_1_3_3_26_2","first-page":"181","article-title":"Analysis of renal handling of radiopharmaceuticals","volume":"46","author":"Trejtnar F","year":"2002","unstructured":"F Trejtnar, M Laznicek, Analysis of renal handling of radiopharmaceuticals. 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