{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:41:19Z","timestamp":1772757679711,"version":"3.50.1"},"reference-count":33,"publisher":"Proceedings of the National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,30]]},"abstract":"<jats:p>\n            The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement\n            <jats:sup>18<\/jats:sup>\n            F-FDG. Copper-64 (\n            <jats:sup>64<\/jats:sup>\n            Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high\n            <jats:italic>in vivo<\/jats:italic>\n            lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-\n            <jats:italic>N<\/jats:italic>\n            -(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific\n            <jats:sup>64<\/jats:sup>\n            Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with\n            <jats:sup>64<\/jats:sup>\n            Cu resulted in &gt;95% of the\n            <jats:sup>64<\/jats:sup>\n            Cu being chelated by the immunoconjugate. Specific activities of at least 10 \u03bcCi\/\u03bcg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after\n            <jats:sup>64<\/jats:sup>\n            Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15\u201320% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5\u201310% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (&lt;5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The\n            <jats:sup>64<\/jats:sup>\n            Cu-SarAr-mAb system described here is potentially applicable to\n            <jats:sup>64<\/jats:sup>\n            Cu-PET imaging with a broad range of antibody or peptide-based imaging agents.\n          <\/jats:p>","DOI":"10.1073\/pnas.0708436104","type":"journal-article","created":{"date-parts":[[2007,10,22]],"date-time":"2007-10-22T23:11:54Z","timestamp":1193094714000},"page":"17489-17493","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":124,"title":["Positron emission tomography (PET) imaging of neuroblastoma and melanoma with\n            <sup>64<\/sup>\n            Cu-SarAr immunoconjugates"],"prefix":"10.1073","volume":"104","author":[{"given":"Stephan D.","family":"Voss","sequence":"first","affiliation":[{"name":"*Department of Radiology and"}]},{"given":"Suzanne V.","family":"Smith","sequence":"additional","affiliation":[{"name":"Australian National Science and Technology Organization (ANSTO), New Illawarra Road, PMB1, Menai, New South Wales 2234, Australia;"}]},{"given":"Nadine","family":"DiBartolo","sequence":"additional","affiliation":[{"name":"Australian National Science and Technology Organization (ANSTO), New Illawarra Road, PMB1, Menai, New South Wales 2234, Australia;"}]},{"given":"Lacey J.","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114;"}]},{"given":"Erika M.","family":"Cyr","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114;"}]},{"given":"Ali A.","family":"Bonab","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114;"}]},{"given":"Jason L. J.","family":"Dearling","sequence":"additional","affiliation":[{"name":"*Department of Radiology and"}]},{"given":"Edward A.","family":"Carter","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114;"}]},{"given":"Alan J.","family":"Fischman","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114;"}]},{"given":"S. Ted","family":"Treves","sequence":"additional","affiliation":[{"name":"*Department of Radiology and"},{"name":"Division of Nuclear Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115;"}]},{"given":"Stephen D.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Lexigen Research Center, EMD\u2013Serono, 45A Middlesex Turnpike, Billerica, MA 01821-3936; and"}]},{"given":"Alan M.","family":"Sargeson","sequence":"additional","affiliation":[{"name":"**Research School of Chemistry, Australian National University, Canberra ACT 0200, Australia"}]},{"given":"James S.","family":"Huston","sequence":"additional","affiliation":[{"name":"Lexigen Research Center, EMD\u2013Serono, 45A Middlesex Turnpike, Billerica, MA 01821-3936; and"}]},{"given":"Alan B.","family":"Packard","sequence":"additional","affiliation":[{"name":"*Department of Radiology and"},{"name":"Division of Nuclear Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115;"}]}],"member":"341","published-online":{"date-parts":[[2007,10,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2312021185"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc882"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(03)00374-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.rlu.0000082674.73719.70"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2004.06.009"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1141"},{"key":"e_1_3_4_7_2","first-page":"1685","volume":"33","author":"Anderson CJ","year":"1992","unstructured":"CJ Anderson, JM Connett, SW Schwarz, PA Rocque, LW Guo, GW Philpott, KR Zinn, CF Meares, MJ Welch J Nucl Med 33, 1685\u20131691 (1992).","journal-title":"J Nucl Med"},{"key":"e_1_3_4_8_2","first-page":"3207s","volume":"5","author":"Connett JM","year":"1999","unstructured":"JM Connett, TL Buettner, CJ Anderson Clin Cancer Res 5, 3207s\u20133212s (1999).","journal-title":"Clin Cancer Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.150228297"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc990167l"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(98)00017-1"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(04)86011-7"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/b103242a"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1351\/pac198456111603"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00354a067"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-8545(95)01218-4"},{"key":"e_1_3_4_17_2","first-page":"G1400","volume":"272","author":"Bingham MJ","year":"1997","unstructured":"MJ Bingham, AM Sargeson, HJ McArdle Am J Physiol 272, G1400\u2013G1407 (1997).","journal-title":"Am J Physiol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0883-2897(91)90095-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1039\/b605615f"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(84)90435-6"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8051(95)02001-2"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(99)00026-8"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5702"},{"key":"e_1_3_4_24_2","first-page":"1577","volume":"28","author":"Cheung NK","year":"1987","unstructured":"NK Cheung, JE Neely, B Landmeier, D Nelson, F Miraldi J Nucl Med 28, 1577\u20131583 (1987).","journal-title":"J Nucl Med"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0227"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4472"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1480"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(99)00049-9"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm030383m"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2004.s.002"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(89)90093-8"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.7.1936.1936"},{"key":"e_1_3_4_33_2","unstructured":"NM Di Bartolo (Australian Natl Univ Canberra Australia PhD thesis. 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