{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:49:10Z","timestamp":1792129750285,"version":"4.4.0"},"reference-count":17,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[1990,9,1]],"date-time":"1990-09-01T00:00:00Z","timestamp":652147200000},"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":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[1990,9]]},"abstract":"\n A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t\u2020 after which a plot of f\n t<\/jats:sup>\n 0<\/jats:sub>\n ROI( t') dt'\/ROI( t) versus f\n t<\/jats:sup>\n 0<\/jats:sub>\n C\n p<\/jats:sub>\n ( t') dt'\/ROI( t) (where ROI and C\n p<\/jats:sub>\n are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume, V\n p<\/jats:sub>\n . For a two-compartment model, the slope is given by \u03bb + V\n p<\/jats:sub>\n , where \u03bb is the partition coefficient and the intercept is \u22121\/[ k\n 2<\/jats:sub>\n (1 + V\n p<\/jats:sub>\n \/\u03bb)]. For a three-compartment model, the slope is \u03bb(1 + B\n max<\/jats:sub>\n \/ K\n d<\/jats:sub>\n ) + V\n p<\/jats:sub>\n and the intercept is \u2212{(1 + B\n max<\/jats:sub>\n \/ K\n d<\/jats:sub>\n )\/ k\n 2<\/jats:sub>\n + [ k\n off<\/jats:sub>\n (1 + K\n d<\/jats:sub>\n \/ B\n max<\/jats:sub>\n )]\n \u22121<\/jats:sup>\n } [1 + V\n p<\/jats:sub>\n \/\u03bb(1 + B\n max<\/jats:sub>\n \/ K\n d<\/jats:sub>\n )]\n \u22121<\/jats:sup>\n (where B\n max<\/jats:sub>\n represents the concentration of ligand binding sites and K\n d<\/jats:sub>\n the equilibrium dissociation constant of the ligand\u2013binding site complex, k\n off<\/jats:sub>\n ( k\n 4<\/jats:sub>\n ) the ligand\u2013binding site dissociation constant, and k\n 2<\/jats:sub>\n is the transfer constant from tissue to plasma). This graphical method provides the ratio B\n max<\/jats:sub>\n \/ K\n d<\/jats:sub>\n from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI\/ C\n p<\/jats:sub>\n is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from [ N-methyl-\n 11<\/jats:sup>\n C]-(\u2013)-cocaine ([\n 11<\/jats:sup>\n C]cocaine) studies in normal human volunteers and the results are compared to the standard nonlinear least-squares analysis. The calculated value of B\n max<\/jats:sub>\n \/ K\n d<\/jats:sub>\n for the high-affinity binding site for cocaine is 0.62 \u00b1 0.20, in agreement with literature values.\n <\/jats:p>","DOI":"10.1038\/jcbfm.1990.127","type":"journal-article","created":{"date-parts":[[2011,4,8]],"date-time":"2011-04-08T13:02:57Z","timestamp":1302267777000},"page":"740-747","source":"Crossref","is-referenced-by-count":1272,"title":["Graphical Analysis of Reversible Radioligand Binding from Time\u2014Activity Measurements Applied to [\n N<\/i>\n -\n 11<\/sup>\n C-Methyl]-(\u2212)-Cocaine PET Studies in Human Subjects"],"prefix":"10.1177","volume":"10","author":[{"given":"Jean","family":"Logan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna S.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred P.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Dewey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Schlyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"MacGregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hitzemann","sequence":"additional","affiliation":[{"name":"State University of New York at Stony Brook, Stony Brook, and Psychiatry Service, Veterans Administration Medical Center, Northport, New York, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Bendriem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. John","family":"Gatley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Christman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[1990,9,1]]},"reference":[{"key":"bibr1-jcbfm.1990.127","first-page":"347","volume-title":"Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart","author":"Carson RE","year":"1986"},{"key":"bibr2-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890040412"},{"key":"bibr3-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1989.59"},{"key":"bibr4-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1981.tb00587.x"},{"key":"bibr5-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(82)90018-2"},{"key":"bibr6-jcbfm.1990.127","first-page":"223","volume-title":"PET and NMR: New Perspectives in Neuroimaging and in Clinical Neurochemistry","author":"Gjedde A","year":"1986"},{"key":"bibr7-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1983.tb13666.x"},{"key":"bibr8-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1987.tb13129.x"},{"key":"bibr9-jcbfm.1990.127","first-page":"898","volume":"30","author":"Logan J","year":"1989","journal-title":"J Nucl Med"},{"key":"bibr10-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410150302"},{"key":"bibr11-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1983.1"},{"key":"bibr12-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.87"},{"key":"bibr13-jcbfm.1990.127","first-page":"328","volume":"20","author":"Phelps ME","year":"1979","journal-title":"J Nucl Med"},{"key":"bibr14-jcbfm.1990.127","volume-title":"Numerical Recipes. The art of Scientific Computing","author":"Press WH","year":"1986"},{"key":"bibr15-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1007\/BF00501873"},{"key":"bibr16-jcbfm.1990.127","unstructured":"Shampine LF, Gordon MK, (1975) Computer Solution of Ordinary Differential Equations: The Initial Value Problem. San Francisco, W.H. Freeman, pp. 289\u2013293"},{"key":"bibr17-jcbfm.1990.127","doi-asserted-by":"publisher","DOI":"10.1126\/science.6334363"}],"container-title":["Journal of Cerebral Blood Flow & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.1990.127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.1990.127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:07:17Z","timestamp":1777493237000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/jcbfm.1990.127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,9]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1990,9]]}},"alternative-id":["10.1038\/jcbfm.1990.127"],"URL":"https:\/\/doi.org\/10.1038\/jcbfm.1990.127","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,9]]}}}