Positron emission tomography with [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA) was used to examine the integrity of the blood–brain barrier (BBB) in five patients with dementia of the Alzheimer type and in five healthy age-matched controls. Within a scanning time of 90 min, there was no evidence that measurable intravascular tracer entered the brain in either the dementia or the control group. An upper limit for the cerebrovascular permeability–surface area product of [68Ga]EDTA was estimated as 2 × 10−6 S−1 in both groups. The results provide no evidence for breakdown of the BBB in patients with dementia of the Alzheimer type.
American Psychiatric Association, Task Force on Nomenclature and Statistics (1980) Diagnostic and Statistical Manual for Mental Disorders, 3rd ed.Washington, D.C., American Psychiatric Association
2.
BeckJVArnoldKJ, (1977) Parameter Estimation in Engineering and Science. New York, John Wiley & Sons, pp 386–387
3.
BlasbergRGWrightDCPatlakCSBrooksRACarsonREGroothiusDRDi ChiroG, (1984) Determination of regional blood-tissue transfer constants and initial (plasma) volume in brain and brain tumors using 68Ga-EDTA and dynamic position emission tomography. J Nucl Med25:P51
4.
CarsonREHuangSCPhelpsME, (1981) BLD: A software system for physiological data handling and model analysis. Proceedings Fifth Ann Symp on Computer Applications in Medical Care, IEEE Computer Soc, pp 562–565
5.
CroneC, (1963) The permeability of capillaries in various organs as determined by use of the “indicator diffusion” method. Acta Physiol Scand58:292–305
6.
DuaraRMargolinRARobertson-TchaboEALondonEDSchwartzMRenfrewJWKoziarzBJSundaramMGradyCMooreAMIngvarDHSokoloffLWeingartnerHKesslerRMManningRGChanningMACutlerNRRapoportSI, (1983) Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years. Brain106:761–775
7.
EdwardsonLAOakleyAEKlinowskiJPerryRHPerryEKCandyJM, (1985) Aluminosilicates and the genesis of senile plaques. Soc Neurosci Abstr11:168
8.
EikelenboomPStamFC, (1984) An immunohistochemical study on cerebral vascular and senile plaque amyloid in Alzheimer's dementia. Virchows Arch [Cell Pathol]47:17–25
9.
EricsonKBergströmMErikssonLHatemAGreitzTSöderströmCEWidenL, (1981) Positron emission tomography with 68Ga-EDTA compared with transmission computed tomography in the evaluation of brain infarcts. Acta Radiol [Diagn] (Stockh)22:385–398
10.
EycleshymerACSchoemakerDM, (1911) A Cross-Section Anatomy. New York, Appleton, pp 2–55
11.
FenstermacherJDRapoportSI, (1984) Blood-brain barrier. In: Handbook of Physiology, Sect 2, The Cardiovascular System, Vol 4: Microcirculation, Pt 2 (RenkinEWMichelCC, eds), Bethesda, American Physiological Society, pp 969–1000
12.
FolsteinMFFolsteinSEMcHughPR, (1975) “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res12:189–198
13.
FriedlandRPYanoYBudingerTFGanzEHuesmanRHDerenzoSEKnittelB, (1983) Quantitative evaluation of blood brain barrier integrity in Alzheimer-type dementia: Positron emission tomographic studies with rubidium-82. Eur Neurol22(suppl 2): 19
FriedlandRPJagustWJBudingerTFYanoYHuesmanRHKnittelB, (1985b) Dynamic PET studies of blood-brain barrier permeability in Alzheimer's disease. J Nucl Med26:P103
16.
GlennerGGHenryJHFujiharaS, (1981). Congophilic angiopathy in the pathogenesis of Alzheimer's degeneration. Ann Pathol1:120–129
17.
HawkinsRAPhelpsMEHuangS-CWapenskiJAGrimmPOParkerRGJuillardGGreenbergP, (1984a) A kinetic evaluation of blood–brain barrier permeability in human brain tumors with [68Ga]EDTA and positron computed tomography. J Cereb Blood Flow Metab4:507–515
18.
HawkinsRAPhelpsMEHuangS-CWapenskiJAGrimmPDGreenbergPParkerRGJuillardGKuhlDE, (1984b) Simultaneous estimations of blood brain barrier (BBB) permeability and local cerebral blood volume (CBV) in human brain tumors with positron tomography and Ga-68 EDTA. J Nucl Med25:P9
19.
HaxbyJVDuaraRGradyCLCutlerNRRapoportSI, (1985) Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease. J Cereb Blood Flow Metab5:193–200
20.
HerscovitchPAuchusAPGadoMChiDRaichleME, (1986) Correction of positron emission tomography data for cortical atrophy. J Cereb Blood Flow Metab6:120–124
21.
IlsenHWSatoMPawlikGHerholzKWienhardKHeissW-D, (1984) (68Ga)-EDTA positron emission tomography in the diagnosis of brain tumors. Neuroradiology26:393–398
22.
IshiiTHagaS, (1976) Immuno-electron-microscopic localization of immunoglobulins in amyloid fibrils of senile plaques. Acta Neuropathol (Berl)36:243–249
23.
IshiiTHagaS, (1984) Immuno-electron-microscopic localization of complements in amyloid fibrils of senile plaques. Acta Neuropathol (Berl)63:296–300
24.
IshiiTHagaSShimizuF, (1975) Identification of components of immunoglobulins in senile plaques by means of fluorescent antibody technique. Acta Neuropathol (Berl)32:157–162
25.
JardenJODhawanVKearfottKJRottenbergDA, (1984) Measurement of brain/tumor capillary permeability using 82Rb and positron emission tomography. Ann Neurol16:131
26.
JardenJODhawanVPosnerJBRottenbergDA, (1985) The effect of corticosteroids on the blood-brain/tumor barrier: Quantitative in vivo measurements using 82Rb and positron emission tomography. Neurology35(suppl 1):289
27.
KayADPapadopoulosNMCostelloRMayCAtackJRLuxenbergJSCutlerNRRapoportSI, (1986) Cerebrospinal fluid and serum concentrations of albumin and immunoglobulin G in patients with Alzheimer's disease: Correlation with cerebral atrophy and intracranial volume. Neurobiol Aging (in press)
28.
KesslerRMGobleJCBirdJHGirtonMEDoppmanJLRapoportSIBarrangerJA, (1984) Measurement of blood–brain barrier permeability with positron emission tomography and [68Ga]EDTA. J Cereb Blood Flow Metab4:323–328
29.
KlatzoIChuiEFujiwaraKSpatzM, (1980) Resolution of vasogenic brain edema. Adv Neurol28:359–373
30.
LivingstonRB, (1955) Cerebrospinal fluid. In: A Textbook of Physiology (FultonJF, ed), Philadelphia, WB Saunders, pp 950–963
31.
MannDMADaviesJSHawkesJYatesPO, (1982) Immunohistochemical staining of senile plaques. Neuropathol Appl Neurobiol8:55–61
32.
MattisS, (1976) Mental status examination for organic mental syndrome in the elderly patient. In: Geriatric Psychiatry (BellakLKarasuTB, eds), New York, Grune & Stratton, pp 77–121
33.
NandyK, (1978) Brain-reactive antibodies in aging and senile dementia. In: Aging, Vol 7: Alzheimer's Disease: Senile Dementia and Related Disorders (KatzmanRTerryRDBickKL, eds), New York, Raven Press, pp 503–512
34.
OhnoKPettigrewKDRapoportSI, (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol235:H299–H307
35.
PatlakCSBlasbergRGFenstermacherJD, (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab3:1–7
36.
PearsonRCAEsiriMMHiornsRWWilcockGKPowellTPS, (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease. Proc Natl Acad Sci82:4531–4534
37.
RapoportSI, (1976) Blood–Brain Barrier in Physiology and Medicine. New York, Raven Press
38.
RapoportSI, (1978) A mathematical model for vasogenic brain edema. J Theor Biol74:439–467
39.
RapoportSI, (1985) A model for brain edema. In: Brain Edema, Proceedings of the Sixth International Symposium (InabaYKlatzoISpatzM, eds), Berlin, Springer-Verlag, pp 59–71
40.
RapoportSIFredericksWROhnoKPettigrewKD, (1980) Quantitative aspects of reversible osmotic opening of the blood-brain barrier. Am J Physiol238:R421–R431
41.
ReeseTSKarnovskyMJ, (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol34:207–217
42.
RenkinEM, (1959) Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles. Am J Physiol197:1205–1210
43.
SchlageterNLHorwitzBCreaseyHCarsonRDuaraRBergGWRapoportSI, (1986) Relation of measured brain glucose utilization and cerebral atrophy in man. J Neurol Neurosurg Psychiatry (in press)
44.
SchwartzMCreaseyHGradyCLDeLeoJMFredericksonHACutlerNRRapoportSI, (1985) Computed tomographic analysis of brain morphometries in 30 healthy men, aged 21 to 81 years. Ann Neurol17:146–157
45.
SiesjöBK, (1978) Brain Energy Metabolism. Chichester, John Wiley & Sons, p 174
46.
SorensonSC, (1974) The permeability to small ions of tight junctions between cerebral endothelial cells. Brain Res70:174–178
47.
WapenskiJAHawkinsRAMazziotaJCPhelpsMEHuangS-CVerityA, (1985) Relationship of blood-brain barrier (BBB) permeability by Ga-68 EDTA positron tomography with characteristics of human brain tumors. Neurology35(suppl 1):288
48.
WisnièwskiHMKozlowskiPB, (1982) Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT). Ann NY Acad Sci396: 119–129
49.
WongDFInoueYRosenbloomSWharamMCarsonBWagnerHNJr, (1984) Gallium-68 ethylenediamine tetra-acetic acid (EDTA) imaging of brain tumors by positron tomography. J Nucl Med25:P50–P51
