{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:25:56Z","timestamp":1791177956629,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T00:00:00Z","timestamp":1208217600000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Contrast Media &amp; Molecular"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gd<jats:sub>3<\/jats:sub>L is a trinuclear Gd<jats:sup>3+<\/jats:sup> complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H<jats:sub>12<\/jats:sub>L is based on a trimethylbenzene core bearing three methylene\u2010diethylenetriamine\u2010 <jats:italic>N,N,N<\/jats:italic>\u2033,<jats:italic>N<\/jats:italic>\u2033\u2010tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd<jats:sub>3<\/jats:sub>L has remarkable proton relaxivities at high magnetic field (<jats:italic>r<\/jats:italic><jats:sub>1<\/jats:sub>\u2009=\u200910.2 vs 3.0\u2009m<jats:sc>M<\/jats:sc><jats:sup>\u22121<\/jats:sup>\u2009s<jats:sup>\u22121<\/jats:sup> for GdDOTA at 9.4\u2009T, 37\u00b0C, in H<jats:sub>2<\/jats:sub>O). Here we report an <jats:italic>in vivo<\/jats:italic> MRI feasibility study, complemented with dynamic <jats:italic>\u03b3<\/jats:italic> scintigraphic imaging and biodistribution experiments using the <jats:sup>153<\/jats:sup>Sm\u2010enriched analog. MRI experiments were performed at 9.4\u2009T in mice with Gd<jats:sub>3<\/jats:sub>L and the commercial contrast agent gadolinium(III)\u20101,4,7,10\u2010tetraazacyclododecane\u20101,4,7,10\u2010tetraacetate (GdDOTA). Gd<jats:sub>3<\/jats:sub>L was well tolerated by the animals at the dose of 8\u2009\u00b5mol\u2009Gd\u2009kg<jats:sup>\u22121<\/jats:sup> body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd<jats:sub>3<\/jats:sub>L injection than after GdDOTA injection at an identical dose. The relaxation rates, \u0394<jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub>, were calculated from the IR TrueFISP data. During the excretory phase, the \u0394<jats:italic>R<\/jats:italic><jats:sub>1<\/jats:sub> for various tissues was similar for Gd<jats:sub>3<\/jats:sub>L and GdDOTA, when the latter was injected at a three\u2010fold higher dose (24 vs 8\u2009\u00b5mol\u2009Gd\u2009kg<jats:sup>\u22121<\/jats:sup> body weight). These results point to an approximately three times higher <jats:italic>in vivo<\/jats:italic> relaxivity (per Gd) for Gd<jats:sub>3<\/jats:sub>L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined <jats:italic>in vitro<\/jats:italic> is retained under <jats:italic>in vivo<\/jats:italic> conditions. They also indicate that the two inner sphere water molecules per Gd in Gd<jats:sub>3<\/jats:sub>L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd<jats:sub>3<\/jats:sub>L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic <jats:italic>\u03b3<\/jats:italic> scintigraphic studies and the biodistribution experiments performed in Wistar rats with <jats:sup>153<\/jats:sup>Sm\u2010enriched <jats:sup>*<\/jats:sup>Sm<jats:sub>3<\/jats:sub>L are also indicative of a fast elimination via the kidneys. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cmmi.233","type":"journal-article","created":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T15:52:33Z","timestamp":1208274753000},"page":"78-85","source":"Crossref","is-referenced-by-count":37,"title":["<i>In vivo<\/i> MRI assessment of a novel Gd<sup>III<\/sup>\u2010based contrast agent designed for high magnetic field applications"],"prefix":"10.1002","volume":"3","author":[{"given":"Paulo Loureiro","family":"de Sousa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Bruno","family":"Livramento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Helm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 E.","family":"Merbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"M\u00eame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bich\u2010Thuy","family":"Doan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Claude","family":"Beloeil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I. M.","family":"Prata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F. G.","family":"C. Geraldes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"T\u00f3th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,4,15]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00016.2004"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr980440x"},{"key":"e_1_2_1_4_2","volume-title":"The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging","author":"Merbach AE","year":"2001"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/b510982p"},{"key":"e_1_2_1_6_2","first-page":"45","volume-title":"The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging","author":"T\u00f3th E","year":"2001"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200461875"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200500969"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmmi.92"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/b717390c"},{"key":"e_1_2_1_11_2","first-page":"243","volume-title":"The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging","author":"Br\u00fccher E","year":"2001"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic0500309"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic00110a019"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-198809001-00049"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199303001-00004"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0730-725X(00)00134-X"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20336"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10347"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0730-725X(95)02097-D"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2586(200008)12:2<289::AID-JMRI11>3.0.CO;2-O"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10327"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/b007901o"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(02)00417-8"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.rli.0000084891.15996.0f"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20058"},{"key":"e_1_2_1_25_3","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20208"}],"container-title":["Contrast Media &amp; Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmmi.233","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmmi.233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T19:13:39Z","timestamp":1700075619000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cmmi.233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1002\/cmmi.233"],"URL":"https:\/\/doi.org\/10.1002\/cmmi.233","archive":["Portico"],"relation":{},"ISSN":["1555-4309","1555-4317"],"issn-type":[{"value":"1555-4309","type":"print"},{"value":"1555-4317","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3]]}}}