EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells.

AIM: To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. METHODOLOGY: Dentine discs prepared from extracted human molars were pre-treated with EDTA (10%), NaOCl (5.25%) or H2 O. Migration of dental pulp stem cells towards pre-treated dentine after 24 and 48 h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pre-treated dentine for 7 days was determined by RT-qPCR. Nonparametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time-points (Mann-Whitney U-test, α = 0.05). RESULTS: Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (P = 0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pre-treated dentine discs. CONCLUSIONS: EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pre-treatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favourably on new tissue formation within the root canal.

[123I]IPCIT and [123I]beta-CIT as SPECT tracers for the dopamine transporter: a comparative analysis in nonhuman primates.

[123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]-CIT) and its isopropylester analog [123I]PCIT, both of which are phenyltropane derivatives of cocaine with high affinity for the dopamine (DA) transporter, were compared using single photon emission computed tomography in nonhuman primates. Although IPCIT is significantly more selective for the DA transporter than beta-CIT, striatal distribution volumes of specifically bound tracer were similar for both tracers. Compartmental modeling results were compared with a simple peak equilibrium method used previously by this group. The peak equilibrium method is shown to overestimate striatal distribution volumes, primarily due to a difference in the calculated time of peak specific uptake.

Ferenczi's fatal illness in historical context.

In August 1932, Ferenczi was already manifesting symptoms of his fatal illness, pernicious anemia. This was diagnosed between September 20 and October 2 of that year, less than a month after the Twelfth International Psychoanalytic Congress in Wiesbaden. Despite seemingly successful treatment with injectable liver extract, he underwent an acute psychotic episode in March 1933, triggered by the neurological symptoms of his illness. These facts substantiate the subsequent claim of Freud and Jones that Ferenczi suffered from paranoia near the end of his life, but they do not support the commonly-held view that the writings and experiments in psychoanalytic technique of his last five years were symptomatic of a progressive mental illness.

Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease.

BACKGROUND: The apolipoprotein E (Apo E) epsilon4 allele has been associated with parietal metabolic abnormalities and asymmetries in asymptomatic subjects at risk for Alzheimer disease (AD). However, previous research has shown minimal effect of the epsilon4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD. OBJECTIVE: To determine whether the Apo E epsilon4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD. PATIENTS AND METHODS: Thirty patients with AD with the epsilon4 allele (epsilon4+ AD), 22 patients with AD without the epsilon4 allele (epsilon4- AD), and 14 healthy control subjects underwent single-photon emission computed tomography (SPECT) scanning with 740 MBq technetium Tc 99m hexamethylpropyleneamine oxime. Ratios of parietal-unaffected regions and a left-right parietal asymmetry index were compared between both patient groups. RESULTS: The group with epsilon4- AD was younger (P = .005, Student t test) and had an earlier age of onset (P = .005) than the group with epsilon4+ AD. Analysis of covariance revealed no significant difference in the parietal rCBF ratio, controlling for age of onset and Mini-Mental State Examination score (F(1,48) = 0.06; P = .81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with epsilon4- AD (mean +/- SD, 9.7% +/- 5.5%) than those with epsilon4+ AD (6.3% +/- 4.7%; F(1,50) = 5.89; P = .02; analysis of variance). When number of epsilon4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 epsilon4 allele copies. An exploratory analysis of multiple cortical structures suggested that this asymmetry extended to additional regions (superior temporal) and to combined association cortex. CONCLUSIONS: Greater parietal rCBF asymmetry is involved in epsilon4- AD than in epsilon4+ AD. Lack of the epsilon4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.

DET1 represses a chloroplast blue light-responsive promoter in a developmental and tissue-specific manner in Arabidopsis thaliana.

The chloroplast psbD-psbC loci, which encode the D2 and CP43 subunits of the photosystem II reaction center, respectively, are regulated by a blue light-responsive promoter (BLRP). It has recently been shown in barley seedlings that activation of psbD-psbC transcription by blue light involves inhibition of a protein kinase that represses the BLRP in the dark. To elucidate further the photosensory pathways regulating the psbD BLRP, the effects of three nuclear mutations on the expression of the BLRP in chloroplasts of Arabidopsis thaliana were examined. The mutants used included the det1-1 and det1-6 alleles for the nuclear protein DET1, involved in repressing photomorphogenesis, and the cry1 gene for the blue light photoreceptor, cryptochrome (CRY1), involved in hypocotyl elongation. The BLRP was not significantly expressed in cotyledons of light-grown wild-type seedlings, unlike the light-responsive expression of the chloroplast, psbA and rbcL, and nuclear, Lhcb and Chs, genes. Analysis of the mutants revealed that DET1 represses transcription from the BLRP in a developmental and tissue-specific manner, which is unique from the effects that DET1 has on other light-regulated promoters. In addition, the cry1 mutation did not reduce the expression of the BLRP in response to blue light. This suggests that the BLRP is regulated by a different photosensory system relative to CRY1. A model is proposed involving blue light, DET1 and phytochrome in regulating transcription from the psbD BLRP.

Structure and blue-light-responsive transcription of a chloroplast psbD promoter from Arabidopsis thaliana.

We characterized the effects of light on psbD transcription and mRNA levels during chloroplast development in Arabidopsis thaliana. After 6 to 12 hours of illumination of dark-grown seedlings, two psbD mRNAs were detected and their 5' ends were mapped to positions -550 and -190 bp upstream from the psbD translational start codon. Their kinetics of accumulation resembled the accumulation of chloroplast psbA and rbcL mRNAs but differed from the accumulation of the nuclear-encoded Lhcb and Chs mRNAs. A third psbD mRNA with its 5' ends at position -950 accumulated after illumination of > 180 h. The 5' ends of this transcript were mapped to a nucleotide sequence that is highly conserved with functional sequences in the barley (Hordeum vulgare) blue-light-responsive promoter (BLRP). Transcription from the Arabidopsis psbD promoter was 3-fold higher in blue relative to red light, whereas red and blue light affected total chloroplast, rbcL, and 16S rDNA transcription similarly. This study shows that transcription of Arabidopsis psbD is mediated by a BLRP and suggests that psbD genes in other land plants are regulated by a common blue-light-signaling pathway. Isolating the BLRP from Arabidopsis will allow molecular genetic studies aimed at identifying the pertinent photoreceptor and components of this phototransduction pathway.

Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients.

UNLABELLED: Iodine-123-beta-CIT has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. We studied the test/retest reproducibility of SPECT measures in Parkinson's disease patients and healthy controls obtained after injection of [123I])beta-CIT in part to assess the utility of this tracer for longitudinal evaluation of striatal dopamine transporters as a marker of disease progression. METHODS: Seven Parkinson's disease patients and seven healthy control subjects participated in two [123I]beta-CIT SPECT scans separated by 7-21 days. Subjects were imaged at 24 hr post injection of 360 MBq (9.7 mCi) of [123I]beta-CIT. Two outcome measures were evaluated; 1) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V3," and 2) the total specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. For both measures, test/retest variability was calculated as the absolute difference of test minus retest divided by the mean of test/retest and expressed as a percent. In addition, the reproducibility of left and right striatal asymmetry and putamen:caudate ratios were determined. RESULTS: The two outcome measures demonstrated excellent test/retest reproducibility for both the Parkinson's disease and healthy subject groups with variability of striatal V3" = 16.8 +/- 13.3% and percent striatal uptake = 6.8 +/- 3.4% for Parkinson's disease patients and V3" = 12.8 +/- 8.9% and %SSU = 7.0 +/- 3.9% for control subjects. There were no statistically significant differences in test/retest variability between control subjects and Parkinson's disease patients for either outcome measure. The reproducibility of left/right asymmetry indices and putamen-to-caudate ratios showed no patient versus control subject differences. The asymmetry index had greater test/retest variability than the other outcome measures. CONCLUSION: These data suggest that SPECT imaging performed at 24 hr postinjection of [123I]beta-CIT permits calculation of reliable and reproducible measures of dopamine transporters in both Parkinson's disease patients and control subjects and supports the feasibility of using [123I]beta-CIT in the evaluation of disease progression in Parkinson's disease.

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.

Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer's disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age +/- SD = 68.9 +/- 8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 +/- 8.0 years) participated. AD patients were scanned with 20 mCi of Tc99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 +/- 5.8%; whereas those treated with placebo showed a decrease of -2.0 +/- 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly "functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.

Preclinical evaluation of [123I]R93274 as a SPECT radiotracer for imaging 5-HT2A receptors.

Studies in rodents have suggested that the radioiodinated 5-HT2A receptor antagonist [123I]R93274 (123-iodine-N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-ami no- 5-iodo-2-methoxybenzamide) (Kd = 0.1 nM) might be a promising single photon emission computerized tomography (SPECT) radiotracer to image 5-HT2A receptors in the living human brain. In this study, we characterized the brain uptake of [123I]R93274 in baboons. Highest brain uptake was observed in cortical areas, while lower uptake was observed in the striatum and the cerebellum. Injection of pharmacological doses of the 5-HT2A receptor antagonist ketanserin resulted in reduction of cortical and striatal radioactivities to the level observed in the cerebellum. Injection of the selective dopamine D2 receptor antagonist raclopride did not affect [123I]R93274 brain uptake. Quantification of 5-HT2A receptors was achieved by measuring the binding potential of 5-HT2A receptors for [123I]R93274 (the binding potential is the product of the density and affinity of available receptors). Regional binding potential values were derived with a three-compartmental kinetic analysis of the time-activity curves in the brain and plasma. Binding potential values of 93 +/- 34 ml/g, 71 +/- 35 ml/g and 31 +/- 11 ml/g were measured in the occipital, temporal and striatal regions, respectively. Similar values were derived using a noncompartmental graphical analysis. These values were in accordance with the in vitro regional distribution of 5-HT2A receptors in primate brain. In conclusion, [123I]R93274 allows visualization and quantification of 5-HT2A receptors in the baboon brain with SPECT.

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates.

The competition between endogenous transmitters and radiolabeled ligands for in vivo binding to neuroreceptors might provide a method to measure endogenous transmitter release in the living human brain with noninvasive techniques such as positron emission tomography (PET) or single photon emission computerized tomography (SPECT). In this study, we validated the measure of amphetamine-induced dopamine release with SPECT in nonhuman primates. Microdialysis experiments were conducted to establish the dose-response curve of amphetamine-induced dopamine release and to document how pretreatment with the dopamine depleter alpha-methyl-para-tyrosine (alpha MPT) affects this response. SPECT experiments were performed with two iodinated benzamides, [123I]IBZM and [123I]IBF, under sustained equilibrium condition. Both radio-tracers are specific D2 antagonists, but the affinity of [123I]IBZM (KD-0.4 nM) is lower than that of [123I]IBF (KD 0.1 nM). With both tracers, we observed a prolonged reduction in binding to D2 receptors following amphetamine injection. [123I]IBZM binding to D2 receptors was more affected than [123I]IBF by high doses of amphetamine, indicating that a lower affinity increases the vulnerability of a tracer to endogenous competition. With [123I]IBZM, we observed an excellent correlation between reduction of D2 receptor binding measured with SPECT and peak dopamine release measured with microdialysis after various doses of amphetamine. Pretreatment with alpha MPT significantly reduced the effect of amphetamine on [123I]IBZM binding to D2 receptors, confirming that this effect was mediated by intrasynaptic dopamine release. Together, these results validate the use of this SPECT paradigm as a noninvasive measurement of intrasynaptic dopamine release in the living brain.

Comparison of technetium-99m-HMPAO and technetium-99m-ECD cerebral SPECT images in Alzheimer's disease.

UNLABELLED: SPECT has shown increasing promise as a diagnostic tool in Alzheimer's disease (AD). Recently, a new SPECT brain perfusion agent, 99mTc-ethyl cysteinate dimer (99mTc-ECD) has emerged with purported advantages in image quality over the established tracer, 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO). This research aimed to compare cerebral images for 99mTc-HMPAO and 99mTc-ECD in discriminating patients with AD from control subjects. METHODS: Twenty-four AD patients (mean age +/- s.d. = 68.9 +/- 8.2 yr) and 13 healthy subjects (68.4 +/- 8.0 yr) were scanned sequentially with 20 mCi of each tracer using the CERASPECT system within 1 mo. Scanning began on average 11.5 +/- 2.8 min after 99mTc-HMPAO injection and 41.8 +/- 10.1 min after 99mTc-ECD. A ratio, R, was derived of count densities in "typically affected" brain structures (parietal and temporal association cortices) to "unaffected" structures (cerebellum, basal ganglia, thalamus, occipital cortex, and sensorimotor cortex). RESULTS: Analysis of variance revealed significant interaction between diagnostic group and radiopharmaceutical (F = 4.71; df = 1.35; p = 0.04), with 99mTc-ECD demonstrating better separation of R values between AD patients and control subjects than 99mTc-HMPAO. Receiver operating characteristic (ROC) analysis, revealed no significant difference in the ability of the two tracers to correctly classify AD patients and control subjects. Both tracers showed high diagnostic accuracy (99mTc-ECD: sensitivity = 100%, specificity = 92%; 99mTc-HMPAO: sensitivity = 100%, specificity = 85%). CONCLUSION: Technetium-99m-ECD shows greater contrast than 99mTc-HMPAO between affected and unaffected brain structures in AD when patients are compared to age-matched control subjects. Both tracers perform equally well in correctly classifying patients and control subjects.

SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT.

Iodine-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) is a useful SPECT tracer for imaging the dopamine transporter. Its slow kinetics, however, necessitate imaging on the day after the injection. Two N-omega-fluoroalkyl analogs of beta-CIT, the fluoropropyl and fluoroethyl compounds (beta-CIT-FP and beta-CIT-FE, respectively), characterized by faster kinetics in baboons, were tested in humans as potential tracers for the dopamine transporter. Four healthy volunteers were injected with [123I]-beta-CIT-FP and another four were injected with [123I]beta-CIT-FE. SPECT data were acquired for 1149 +/- 590 min and 240 +/- 30 min, respectively. Both tracers demonstrated high brain uptake (6.37% +/- 0.37% and 7.8% +/- 1.5% of the injected dose, respectively). Activity concentrated with time in the striatal area, reaching a peak within 30 min, with little or no washout for [123I]beta-CIT-FP and a faster washout for [123I]beta-CIT-FE (14.7% +/- 6.9%). Occipital and midbrain activity showed similar patterns, displaying a peak within 15 min and rapid washout, followed by stable levels at approximately 100 min for both tracers. The ratio of peak specific striatal-to-peak specific midbrain activity was 9.1 +/- 1.8 for [123I]beta-CIT-FP and 7.7 +/- 0.7 for [123I]beta-CIT-FE, showing high in vivo selectivity for the dopamine transporter. These preliminary results suggest that both compounds could be used as SPECT (labeled with 123I) or PET (labeled with 18F) radiotracers to image the dopamine transporters in the living human brain.

Comparison of nifedipine GITS and hydrochlorothiazide in the management of elderly patients with stage I-III diastolic hypertension.

A randomized, double blind, parallel study was performed to compare the effects of nifedipine gastrointestinal therapeutic system (GITS) to hydrochlorothiazide (HCTZ) in the management of the elderly hypertensive. Eighteen patients, mean age 65 +/- 5 years, with Stage I-III diastolic hypertension (sitting diastolic BP between 90 and 115 mm HG) were included in each treatment group. Following a 2 to 8 week placebo washout phase, patients received either nifedipine GITS or HCTZ and were titrated over 5 weeks to achieve a goal diastolic blood pressure less than 90 mm Hg. Patients were then continued on medication during an 8 week maintenance phase. Treatment effect on systolic and diastolic blood pressure was assessed. Serum electrolytes, lipids, blood urea nitrogen, and creatinine were measured before and after treatment. Posttreatment changes in renal and cardiovascular function, as well as left ventricular mass were evaluated. The results showed significant reductions in systolic and diastolic blood pressure with both drugs; no treatment difference was found, although goal blood pressure was achieved more rapidly with nifedipine GITS (28 v 34 days, P < .05). BUN was significantly increased only after diuretic therapy (P < .01) and serum potassium fell to a greater degree with HCTZ (0.3 mEq/L v 0.1 mEq/L) than with nifedipine GITS. No statistically significant changes in left ventricular mass, ejection fraction, glomerular filtration rate, or renal blood flow were seen after therapy with either drug. However, the time peak LV diastolic filling rate decreased with nifedipine GITS (197 to 164 msec) and increased with HCTZ (172 to 198 msec). This treatment difference approached statistical significance (P = .07). Adverse side effects of treatment were reported by 50% of nifedipine GITS patients and 28% of patients treated with HCTZ. This treatment difference was not statistically significant. We conclude that both nifedipine GITS and HCTZ monotherapy provide significant blood pressure reduction in older hypertensives with Stage I-III diastolic hypertension. Both drugs are well tolerated with no significant adverse effect on renal or cardiovascular function after short term therapy.

Reproducibility of iodine-123-beta-CIT SPECT brain measurement of dopamine transporters.

UNLABELLED: Iodine-123-beta-CIT has been used as a probe of monoamine transporters in human and nonhuman primates utilizing SPECT. To assess the utility of this tracer for measurement of striatal dopamine (DA) transporters in human disease, we studied the test/retest variability and reliability of SPECT measures obtained after bolus injection of [123I]beta-CIT 0-7 hr (Day 1) and 18-24 hr (Day 2) after administration. METHODS: For the Day 2 study, seven healthy humans (4 men, 3 women; aged 19-74 yr) participated in two [123I]beta-CIT SPECT scans separated by 7-14 days. Subjects were imaged at 18, 21 and 24 hr postinjection of 370 MBq (10 mCi) [123I]beta-CIT. Two outcome measures were evaluated: (a) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V"3 and (b) the total, specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. Test/retest variability associated with V"3 and total specific striatal uptakes were compared for scans acquired at 18, 21 and 24 hr with 24 hr only postinjection scans. For the Day 1 study, three of the subjects participated in two kinetic studies of [123I]beta-CIT uptake. A three-compartment model was used for determination of konBmax and binding potential (BP = Bmax/Kd) and the reproducibility of the measures assessed. RESULTS: In the Day 2 study, both outcome measures demonstrated excellent test/retest reproducibility with variability of V"3 = 6.8 +/- 6.8% and percent striatal uptake = 6.6 +/- 4.3% using data acquired from all time points. There were no significant differences in variability for the two outcome measures obtained. The intraclass correlation coefficient rho was 0.96 and 0.98 for V"3 and %SSU, respectively. Considering the 24 hr postinjection scans only, there was a nonsignificant trend toward lower test/retest variability for %SSU compared to V"3 (6.6 +/- 4.2% and 12.8 +/- 9.0%, respectively). The test/retest variability for the Day 1 kinetic modeling data showed marked differences depending on the fitting strategy and assumptions about the reversibility of [123I]beta-CIT in striatum. Using a model that assumed a low, fixed value for reversible striatal binding (k4) produced low variability (12 +/- 9%). CONCLUSION: These data suggest that SPECT imaging performed at either 0-7 hr or 18-24 hr after [123I]beta-CIT injection permits calculation of reliable and reproducible measures of dopamine transporters and supports the feasibility of using [123I]beta-CIT in serial evaluation of human neuropsychiatric disease.

Continuous intravenous infusion of iodine-123-IBZM for SPECT determination of human brain dopamine receptor occupancy by antipsychotic agent RWJ-37796.

UNLABELLED: PET has shown that dose-dependent in vivo occupancy of dopamine receptors by antipsychotic drugs is associated with clinical response to antipsychotic agents and the production of extrapyramidal side effects. We studied the feasibility of administering [123I]IBZM as a bolus plus continuous infusion over 8 hr to achieve unchanging regional brain activity levels, and the application of [123I]IBZM continuous infusion to examine the effects of the antipsychotic agent RWJ-37796, on striatal activity in humans. METHODS: Five healthy male subjects received a bolus of [123I]IBZM followed by a continuous infusion at a bolus (mCi):infusion (mCi/hr) ratio of 6:1. Serial SPECT images were obtained every 2-3 min for a total of 8 hr with a 1-2 hr break in the scanning session. Serial venous blood samples were obtained every 30 min for the duration of the study. All five subjects achieved unchanging plasma [123I]IBZM and striatal brain-activity levels over the 300-420 min postinitiation of tracer infusion. Two subjects achieved flat brain time-activity curves later than the others, suggesting the bolus-to-infusion ratio was slightly high. An additional six healthy male subjects received a similar bolus plus constant infusion of [123I]IBZM. RWJ-37796 (0.04 mg/kg) was administered intravenously 157 +/- 13.7 min after the initiation of [123I]IBZM infusion. Serial SPECT brain images, serum prolactin and extrapyramidal side effect ratings were obtained for an additional 330 min. RESULTS: All six subjects demonstrated rapid and marked reduction of striatal activity following RWJ-37796 without return of striatal activity to baseline levels over the 5.5 hr of continued [123I]IBZM administration. Estimated receptor occupancy by RWJ-37796 was 57% +/- 5% (range 47%-67%). Prolactin was only transiently increased in all subjects by 1054% +/- 1084% over baseline. One subject experienced moderate extrapyramidal symptoms (akasthisia) during RWJ-37796 injection. CONCLUSION: SPECT imaging during continuous [123I]IBZM infusion provides a powerful within-scan method for determining both temporal binding characteristics and receptor occupancy of striatal dopamine receptors by antipsychotic agents.

[123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease.

We have used in vivo single-photon emission computed tomography (SPECT) of the dopamine transporter with 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) to investigate striatal dopamine transporter loss in patients with early Parkinson's disease (PD). Striatal uptake of ([123I] beta-CIT was compared in eight early-PD patients with exclusively hemi-parkinsonism and eight age- and sex-matched healthy subjects. [123I] beta-CIT striatal uptake was reduced by approximately 53% contralateral and by 38% ipsilateral to the clinically symptomatic side in the hemi-PD patients, compared with the mean striatal uptake in age- and sex-matched healthy subjects. The relative reduction in [123I] beta-CIT uptake in the hemi-PD patients was greater in the putamen than in the caudate. These data demonstrate that SPECT imaging of the dopamine transporter with [123I] beta-CIT can identify patients with PD at the onset of motor symptoms and suggest that this technique also may be useful in identifying individuals with developing dopaminergic pathology before onset of motor symptoms.

Human biodistribution and dosimetry of the SPECT D2 dopamine receptor radioligand [123I]IBF.

The research discussed in this article aimed to characterize better the biodistribution, excretion and radiation dosimetry of the single photon emission computed tomography (SPECT) D2 Dopamine receptor radioligand [123I]IBF. Following administration of 111 +/- 12 MBq [123I]IBF, seven healthy human subjects were scanned serially with a whole body imager over a 48-h period. Transmission images were obtained with a scanning line source for attenuation correction of the emission images. Urine was collected for 48 h to measure the fraction of activity voided by the renal system. Radiation absorbed dose estimates were performed using biokinetic modeling and the Medical Internal Radiation Dose (MIRD) schema. Highest absorbed doses were to the kidney (0.13 +/- 0.02 mGy/MBq) and urinary bladder wall (0.11 +/- 0.01 mGy/MBq). The effective dose equivalent was 0.041 +/- 0.005 mSv/MBq. Peak brain uptake represented 8% of the injected activity. Rapid urinary excretion minimized the absorbed dose to most tissues. The mean cumulative urinary excretion fraction was 69%. Thus [123I]IBF is a promising SPECT agent for imaging the D2 dopamine receptor in humans with high brain uptake and favorable dosimetry.

Euphorigenic doses of cocaine reduce [123I]beta-CIT SPECT measures of dopamine transporter availability in human cocaine addicts.

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [123I]beta-CIT ([123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n = 6) were injected with [123I]beta-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28 +/- 0.03 and 0.56 +/- 0.07 mg/kg) produced significant (P < 0.0005) reductions in the specific to non-specific equilibrium partition coefficient, V3" (6 +/- 6 and 17 +/- 3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED50) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.

Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome.

BACKGROUND & AIMS: Two modalities, contrast echocardiography and lung perfusion scan, are used to identify intrapulmonary vascular dilatation and diagnose hepatopulmonary syndrome (HPS), but a comparison of these two procedures has not been performed. The aim of this study was to compare the use of these diagnostic modalities in detecting intrapulmonary vascular dilatation and diagnosing HPS. METHODS: Forty consecutive outpatients with biopsy-proven cirrhosis had contrast echocardiography, a lung perfusion scan, and arterial blood gases analyzed. RESULTS: Fifteen of 40 cirrhotics (38%) had positive contrast echocardiogram results. Seven patients with positive echocardiogram results had gas exchange abnormalities and could be considered to have HPS (7 of 40 [17.5%]). Three of these patients were hypoxemic and had no concurrent cardiopulmonary disease, and each had positive contrast echocardiogram and lung perfusion scan results and were readily diagnosed as having HPS. The other 4 patients (3 hypoxemic and 1 normoxemic with an elevated alveolar-arterial gradient) had coexisting intrinsic lung disease and/or chest radiograph abnormalities complicating the diagnosis of HPS, and each had positive echocardiogram and negative lung scan results. The remaining 8 patients with positive echocardiogram results had normal lung scan and normal gas exchange results. No patient had positive lung scan and negative contrast echocardiogram results. CONCLUSIONS: Contrast echocardiography is the most useful screening test for intrapulmonary vasodilatation and may be positive more frequently than lung perfusion scans in patients with HPS.