{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:00:13Z","timestamp":1769749213916,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,9,25]],"date-time":"2002-09-25T00:00:00Z","timestamp":1032912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)\u2010molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd\u2010based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd\u2010containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd\u2010containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging\u2010visualization of cells has been addressed by reporting the authors' observations on the cell\u2010internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd\u2010loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd\u2010complexes per cell is 4 \u00b1 1 \u00d7 10<jats:sup>7<\/jats:sup>. Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. J. Magn. Reson. Imaging 2002;16:394\u2013406. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmri.10180","type":"journal-article","created":{"date-parts":[[2002,10,9]],"date-time":"2002-10-09T04:29:26Z","timestamp":1034137766000},"page":"394-406","source":"Crossref","is-referenced-by-count":295,"title":["Insights into the use of paramagnetic Gd(III) complexes in MR\u2010molecular imaging investigations"],"prefix":"10.1002","volume":"16","author":[{"given":"Silvio","family":"Aime","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Cabella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Colombatto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Geninatti Crich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana","family":"Gianolio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Maggioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,9,25]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.219.2.r01ma19316"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr980440x"},{"key":"e_1_2_9_4_2","first-page":"45","volume-title":"The chemistry of contrast agents in medical magnetic resonance imaging","author":"Toth E","year":"2001"},{"key":"e_1_2_9_5_2","first-page":"193","volume-title":"The chemistry of contrast agents in medical magnetic resonance imaging","author":"Aime S","year":"2001"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3765(19991001)5:10<2977::AID-CHEM2977>3.0.CO;2-T"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3765(20000717)6:14<2609::AID-CHEM2609>3.0.CO;2-S"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910170222"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910310102"},{"key":"e_1_2_9_10_2","volume-title":"The chemistry of contrast agents in medical magnetic resonance imaging","author":"Merbach AE","year":"2001"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic00121a024"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar970300u"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/A827019Z"},{"key":"e_1_2_9_14_2","first-page":"383","volume-title":"The chemistry of contrast agents in medical magnetic resonance imaging","author":"Clarkson RB","year":"2001"},{"key":"e_1_2_9_15_2","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/PL00021449","article-title":"Ternary Gd(III)L\u2010HSA adducts: evidence for the replacement of inner\u2010sphere water molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI","volume":"5","author":"Aime S","year":"2000","journal-title":"J Biol Inorg Chem"},{"key":"e_1_2_9_16_2","first-page":"215","article-title":"Modulation of the water exchange rates in [Gd\u2010DO3A] complex by formation of ternary complexes with carboxylate ligands","volume":"1","author":"Aime S","year":"2001","journal-title":"Chem Commun"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic010313a"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja994315u"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm000983a"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(96)00022-9"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1994.1100"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20020315)114:6<1059::AID-ANGE1059>3.0.CO;2-O"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199810000-00007"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1076-6332(98)80109-8"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199712000-00005"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910190231"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004424-199328090-00002"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0598-623"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja984228m"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1162\/153535002753395671"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3765(20011217)7:24<5261::AID-CHEM5261>3.0.CO;2-D"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00170a016"},{"key":"e_1_2_9_33_2","first-page":"155","article-title":"Can receptors be imaged by nuclear magnetic resonance?","volume":"41","author":"Nunn AD","year":"1997","journal-title":"Q J Nucl Med"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8443"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1229"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1095"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(96)00022-9"},{"key":"e_1_2_9_38_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1182\/blood.V71.3.753.753","article-title":"Characteristics and expression of binding sites specific for ferritin H\u2010chain on human cell lines","volume":"71","author":"Fargion S","year":"1988","journal-title":"Blood"},{"key":"e_1_2_9_39_2","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1182\/blood.V78.4.1056.1056","article-title":"Specific binding sites for H\u2010ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control","volume":"78","author":"Fargion S","year":"1991","journal-title":"Blood"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc990168d"},{"key":"e_1_2_9_41_2","doi-asserted-by":"crossref","first-page":"19181","DOI":"10.1016\/S0021-9258(18)37407-6","article-title":"Ferritin iron kinetics and protein turnover in K562 cells","volume":"263","author":"Roberts S","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.2128"},{"key":"e_1_2_9_43_2","first-page":"32","article-title":"Oxygen therapeutics\u2014current concepts","volume":"48","author":"Hill SE","year":"2001","journal-title":"Can J Anesth"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1880070140"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-5521(95)90126-4"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc010002o"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1039\/a900499h"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19991102)38:21<3192::AID-ANIE3192>3.0.CO;2-#"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0103647"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00141a034"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3765(20001016)6:20<3761::AID-CHEM3761>3.0.CO;2-6"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.199707261"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmri.10180","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.10180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T08:31:48Z","timestamp":1694593908000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.10180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,9,25]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2002,10]]}},"alternative-id":["10.1002\/jmri.10180"],"URL":"https:\/\/doi.org\/10.1002\/jmri.10180","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,9,25]]}}}