{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:04Z","timestamp":1777448944227,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Altern Lab Anim"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:p>\n                    A new rational conceptualisation protocol in new isotopic diagnostic agents has been designed to avoid systematic empirical in vivo screening. This protocol is based on multiple regression analysis, in order to determine the pharmacokinetic model capable of explaining in the best possible way the in vivo behaviour of molecules injected into an organism. Nine technetium complexes (\n                    <jats:sup>99m<\/jats:sup>\n                    Tc-L) were synthesised from aminothiol ligand vectors. These complexes were characterised in terms of their physical, chemical and biological in vitro properties, i.e. lipophilicity (P), free fraction unbound to plasmatic proteins (Fu\n                    <jats:sub>p<\/jats:sub>\n                    ), the fraction unbound to blood cells (Fu\n                    <jats:sub>Cb<\/jats:sub>\n                    ), and membrane adsorption fraction (F\n                    <jats:sub>ad<\/jats:sub>\n                    ), an original factor assessed in vitro. Thus, two pharmacokinetic models were tested. The first takes into account the parameters classically used in pharmacokinetics (P, Fu\n                    <jats:sub>p<\/jats:sub>\n                    , Fu\n                    <jats:sub>Cb<\/jats:sub>\n                    ), and the second, in parallel with the first, includes the membrane adsorption rate (polar\/apolar\/polar membrane model). According to the phenomenon of tissular distribution, the explanatory power of the second model, including the F\n                    <jats:sub>ad<\/jats:sub>\n                    , is radically greater than that of the classical model. The comparative adjusted coefficient of determination ([Formula: see text]\n                    <jats:sup>2<\/jats:sup>\n                    ) of the model, including the F\n                    <jats:sub>ad<\/jats:sub>\n                    versus [Formula: see text]\n                    <jats:sup>2<\/jats:sup>\n                    of the first model, are heart (91%\/6%), liver (89%\/47%), spleen (64%\/44%), lung (78%\/26%), kidney (70%\/33%) and brain (73%\/8%), respectively. In addition, as for the myocardium, the membrane adsorption factor seems to be the only predictive factor of the affinity between the myocardium and neutral or cationic molecules. This refutes the generally held view that only cationic molecules could have an affinity with the heart.\n                  <\/jats:p>","DOI":"10.1177\/026119290002800201","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T05:10:33Z","timestamp":1554786633000},"page":"303-314","source":"Crossref","is-referenced-by-count":1,"title":["Conceptualisation of Diagnostic Agents: From Empirical\n                    <i>In Vivo<\/i>\n                    Screening to Rational\n                    <i>In Vitro<\/i>\n                    Predictive Parameters"],"prefix":"10.1177","volume":"28","author":[{"given":"Hafid","family":"Belhadj-Tahar","sequence":"first","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, 31077 Toulouse, France"},{"name":"Centre Anti-Poisons et de Toxicovigilance, CHU Purpan, Place Baylac, 31059 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachid","family":"Boumahdi","sequence":"additional","affiliation":[{"name":"GREMAQ, UMR 5604, Universit\u00e9 des Sciences, Bat. F.'All\u00e9e de Brienne, 31000 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-h\u00e9l\u00e8ne","family":"Darbieu","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS, UPR 8241, 205 route de Narbonne, 31077 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"bibr1-026119290002800201","unstructured":"CometM. & VidalM. (1998). Radiopharmaceutiques, Chimie des Radiotraceurs et Applications Biologiques, pp. 151\u2013669. 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(1996). Distribution Tissulaire des Complexes du Technetium\u201399m. PhD Thesis, University of Grenoble. 125 pp. Grenoble, France."},{"key":"bibr21-026119290002800201","first-page":"2075","volume":"36","author":"Uccelli L.","year":"1996","journal-title":"Journal of Nuclear Medicine"},{"key":"bibr22-026119290002800201","first-page":"160","volume-title":"Fifth International Symposium on Applied Bioinorganic Chemistry, Book of Abstracts","author":"Belhadj-Tahar H.","year":"1999"},{"key":"bibr23-026119290002800201","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(97)00138-8"},{"key":"bibr24-026119290002800201","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8051(93)90047-X"},{"key":"bibr25-026119290002800201","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600830718"},{"key":"bibr26-026119290002800201","unstructured":"RigopulosP. (1968). French Patent 1 521 021."},{"key":"bibr27-026119290002800201","doi-asserted-by":"crossref","unstructured":"RigopulosP. (1970). 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Paris, France: Flammarion."},{"key":"bibr31-026119290002800201","first-page":"197","volume-title":"Technetium in Chemistry and Nuclear Medicine","author":"M\u00fcnze R.","year":"1986"},{"key":"bibr32-026119290002800201","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8051(95)00001-E"},{"key":"bibr33-026119290002800201","first-page":"1892","volume":"30","author":"Walovitch R.C.","year":"1989","journal-title":"Journal of Nuclear Medicine"},{"key":"bibr34-026119290002800201","doi-asserted-by":"publisher","DOI":"10.1039\/an9952000863"}],"container-title":["Alternatives to Laboratory Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/026119290002800201","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/026119290002800201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:39:31Z","timestamp":1777379971000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/026119290002800201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,3]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,3]]}},"alternative-id":["10.1177\/026119290002800201"],"URL":"https:\/\/doi.org\/10.1177\/026119290002800201","relation":{},"ISSN":["0261-1929","2632-3559"],"issn-type":[{"value":"0261-1929","type":"print"},{"value":"2632-3559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,3]]}}}