Parameter and Index Images of Benzodiazepine Receptor Concentration in the Brain

matical compartmental analysis have enabled quantifica tion of receptorconcentrationand ligandaffinityof these receptors in the human brain. All previously described methods, however, are based on the ligand-receptor inter action model, whose usual structureincludes three com partments (plasma, free and bound ligand) and five param eters (the receptor concentration,B@, and four kinetic parameters, including association and dissociation rate constants). The typical approachis to performa kinetic PETexperiment,defineregionsof interest(ROIs)on brain activity maps and deduce the corresponding time-concen tration curves. Depending on the modeling approach im plemented,these curves are used in one of three ways: 1. To calculate an index that presumably correlates with Invivostudiesof Iigand-receptor interactions withPETdataare based on differentapproaches that provideeither quantitative results(receptor density andaffinity) orindices thatareassumed to be correlatedwiththe receptorconcentration. The aimsofthis studyareto obtainparametric images ofbenzodiazeplne recep forconcentration andof fiumazenil affinityandto studytheva IIdityof tworeceptor concentration indexes. Methods:A three comparU@ient Iigand-receA§@or model, (11CJflumazer@I, and expenmental dataobtainedusinga three-injection protocolin human volunteers wereusedtoacquire parametric images. The delayedactivitymethodandthe apparentdistribution volume (estimated usinga two-compartment modet@ werealsotested andtheirresultscompared w@thoseof themufti-injection ap proach.Results: Parametricimagesof receptordensity,affinity andall kineticparai@etere wereobtalned withacceptable vans lioncoeffidents. A correlation between receptor densityandap parentaffinitywasfound(r = 0.83;p < 0.0005). Thecorrelation betweenreceptorconcentration andapparent distilbution vol urns(estimated withthree-andtwo-compartment models,u's- spectively) wasaccessed usingbotha linear(theusualhypc@h esis)anda nor@inear correlation derivedfromthe relationship between the receptor densityandthe affinity.Conclusion:In spite of the complexityof this protocol(threeinjections,a 2-hr experiment bloodsampling anda metabolite study), weshowed thatthemufti-injection approach is suftat@e for parametA±c brain imaging. Byusingthls approach asa reference, wededuced that the distribution volumeanddelayedactivityirnegesare valid methodsin the usualrangeofthe benzodiazepirie receptorcon centrations foundinthehumanbrain.