Imaging serotonin transporters with 123I-ADAM brain SPECT in healthy non-human primates

BACKGROUND: Serotonin transporters (SERTs) play a major role in modulating serotonergic neuronal function and are the target of many antidepressant drugs used in neuro-psychiatric disorders. To gain more information on the temporal distribution of SERTs, 2-([2-([dimethylamino]methyl)phenoxyl]thio)-5-[I]iodophenylamine (I-ADAM) single photon emission computed tomography (SPECT) was utilized in an in vivo imaging study using non-human primates. METHODS: Two female monkeys (Macaca cyclopis) were studied. Eight brain SPECT imaging examinations, each 30 min in duration, were obtained after injection of 185 MBq of I-ADAM. Images were obtained using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. In addition to visual inspection, the radio-uptake and specific uptake ratios (SURs) of midbrain (MB), thalamus (TH), striatum (ST), temporal and frontal cortices and the whole brain in reference to the corresponding magnetic resonance image at the eight time points were measured. The SUR of MB, using cerebellum (CB) as the reference tissue, was calculated as (MB - CB)/CB, in mean counts/pixel. The SURs of the other brain regions were similarly measured. RESULTS: There was relatively high uptake of I-ADAM in the MB and TH, moderate uptake in ST, lower uptake in the cerebral cortex, and almost no uptake in the CB. The image of MB could be easily identified at the first 30 min time point. It appeared that the SURs of MB, TH and ST reached equilibrium around 210 min after injection. No adverse reactions of the primates were found during and after imaging. Brain distribution of I-ADAM in the primate appeared consistent with the known distribution of SERTs. CONCLUSION: In conjunction with a high SUR in MB, TH and ST, we speculate that I-ADAM may be a potential radioligand for SPECT studies of serotonin transporters in humans.     

Biodistribution and imaging with (123)I-ADAM: a serotonin transporter imaging agent.

2-((2-((Dimethylamino)methyl)phenyl)thio)-5-(123)I-iodophenylamine ((123)I-ADAM) is a new radiopharmaceutical that selectively binds the central nervous system serotonin transporters. The purpose of this study was to measure its whole-body biokinetics and estimate its radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacologic safety to be assessed simultaneously. METHODS: The sample included 7 subjects ranging in age from 22 to 54 y old. An average of 12.7 whole-body scans were acquired sequentially on a dual-head camera for up to 50 h after the intravenous administration of 185 MBq (5 mCi) (123)I-ADAM. The fraction of the administered dose in 13 regions of interest (ROIs) was quantified from the attenuation-corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the MIRD technique. SPECT brain scans obtained 3 h after injection were evaluated using an ROI analysis to determine the range of values for the region to cerebellum. RESULTS: There were no pharmacologic effects of the radiotracer on any of the subjects, including no change in heart rate, blood pressure, or laboratory results. Early planar images showed differentially increased activity in the lungs. SPECT images demonstrated that the radiopharmaceutical localized in the midbrain in a distribution that is consistent with selective transporter binding. The dose-limiting organ in both men and women was the distal colon, which received an average of 0.12 mGy/MBq (0.43 rad/mCi) (range, 0.098-0.15 mGy/MBq). The effective dose equivalent and effective dose for (123)I-ADAM were 0.037 +/- 0.003 mSv/MBq and 0.036 +/- 0.003 mSv/MBq, respectively. The mean adult male value of effective dose for (123)I-ADAM is similar in magnitude to that of (111)In-diethylenetriaminepentaacetic acid (0.035 mGy/MBq), half that of (111)In-pentetreotide (0.81 mGy/MBq), and approximately twice that of (123)I-inosine 5'-monophosphate (0.018 mGy/MBq). The differences in results between this study and a previous publication are most likely due to several factors, the most prominent being this dataset used attenuation correction of the scintigraphic data. Region-to-cerebellum ratios for the brain SPECT scans were 1.95 +/- 0.13 for the midbrain, 1.27 +/- 0.10 for the medial temporal regions, and 1.11 +/- 0.07 for the striatum. CONCLUSION: (123)I-ADAM may be a safe and effective radiotracer for imaging serotonin transporters in the brain and the body.     

SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain

IntroductionSerotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2β-carbomethoxy-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane, [¹²³I]p ZIENT, in nonhuman primate brain.MethodsTwo ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [¹²³I]p ZIENT. To evaluate the selectivity of [¹²³I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection.ResultsIn the bolus to constant infusion studies, equilibrium was established by 4–8 h. [¹²³I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35–71% and 129–151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10%).ConclusionThese findings suggest that [¹²³I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.     

Characterization of the binding sites for 123I-ADAM and the relationship to the serotonin transporter in rat and mouse brains using quantitative autoradiography.

Imaging of serotonin transporter (SERT) in the central nervous system may provide an important tool to evaluate some psychiatric disorders. Recently, a novel (123)I-labeled radiotracer, 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ((123)I-ADAM), has been developed that exhibited a high selectivity for SERT. The aim of this study was to characterize the biodistribution and specificity of (123)I-ADAM to SERT using quantitative autoradiography in both control and neurotoxin-treated animals. METHODS: (123)I-ADAM (74 MBq) was injected intravenously into the mice to access its biodistribution in the brain via quantitative autoradiography. Further, rats with serotonin depleted by intraperitoneal injection of p-chloroamphetamine (PCA) were used to evaluate the specificity of (123)I-ADAM to SERT. The levels of biogenic amines were then measured and correlated with quantitative (123)I-ADAM labeling in control and PCA-treated rat brains. RESULTS: The autoradiographic results showed that (123)I-ADAM accumulated in SERT-rich brain areas after systemic injection, including the globus pallidus, thalamus, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala, and raphe nucleus. The dorsal raphe nucleus had the highest initial uptake with a peak specific binding ratio (i.e., [target - cerebellum]/cerebellum) at 120 min after injection. (123)I-ADAM uptake was dramatically decreased in the hippocampus, thalamus, amygdala, geniculate nuclei, hypothalamus, raphe nucleus, and substantia nigra in PCA-lesioned rats. The decrement in radioactivity was more prominent at higher dosages of PCA and was in parallel with the changes in amounts of serotonin and 5-hydroxyindoleacetic acid in the prefrontal cortex. CONCLUSION: This study demonstrates that regional distribution of (123)I-ADAM radioactivity is similar to the SERT localization in both rat and mouse brains. We also validated that destruction on central serotonergic neurons after PCA treatment inhibits the uptake of (123)I-ADAM in serotonin-rich brain regions. High specific binding to SERT in vivo makes (123)I-ADAM an appropriate radiotracer for solitary studies of serotonin functions in living humans.     

Evaluation of the Serotonin Transporter Ligand 123I-ADAM for SPECT Studies on Humans

Imaging serotonin transporters in the living human brain is important in several fields, such as normal psychophysiology, mood disorders, eating disorders, and neurodegenerative disorders. The aim of this study was to compare different kinetic and semiquantitative methods for assessing serotonin transporters using (123)I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) in humans: an arterial plasma input model, simplified and Logan reference tissue models, and standardized uptake value ratios. METHODS: Nine subjects were scanned with dynamic (123)I-ADAM SPECT (mean age, 31 y; range, 24-43 y), and metabolite-corrected arterial input was measured. Tissue reference models (simplified reference tissue model, Logan reference tissue model, and ratio method) were validated against the outcome of a 1-tissue-compartment model, and performance with decreasing scan length was evaluated. The specificity of (123)I-ADAM binding was investigated in a blocking experiment. RESULTS: Binding estimates from the simplified reference tissue and Logan reference tissue models correlated tightly with full kinetic modeling when based on a 240- or 360-min dynamic acquisition (r = 0.99); however, there were slight underestimations (3%-5%), especially in high-binding regions. Application of the ratio method to data from 200 to 240 min overestimated specific binding (on average, by 10% +/- 28%) and correlated only moderately with estimates from the 1-tissue-compartment model (r = 0.94). With an acquisition time of 0-120 min, the Logan model still yielded an acceptable outcome when a fixed clearance rate constant (k2') from the cerebellum was applied. Intravenously injected citalopram was not associated with a decrease in cerebellar binding. A lipophilic metabolite that did not seem to bind specifically to serotonin transporter was seen in 2 of 7 subjects. CONCLUSION: Serotonin transporter binding with (123)I-ADAM SPECT can be assessed with the Logan model based on a 120-min acquisition when a constant k2' is applied. This model, because it allows for more accurate and less biased binding estimates and thus reduces the required sample size, is advantageous over the ratio method used in clinical studies so far. A single blocking experiment supported the use of the cerebellum as a reference region.     

SPECT of serotonin transporters using 123I-ADAM: optimal imaging time after bolus injection and long-term test-retest in healthy volunteers.

(123)I-ADAM (2-([2-([dimethylamino]methyl)phenyl]thio)-5-(123)I-iodophenylamine) has been recently proposed as a new serotonin transporter (SERT) ligand for SPECT. The objective of this study was to characterize (123)I-ADAM in healthy volunteers. (123)I-ADAM distribution in the normal brain, pseudoequilibrium interval after a single injection, normal specific uptake values, and long-term test-retest variability and reliability were investigated. METHODS: Ten healthy volunteers underwent 2 SPECT sessions under the same conditions 47.6 +/- 24.0 d apart. Scans were sequentially acquired from the time of (123)I-ADAM intravenous injection up to 12 h after injection. Regions of interest (ROIs) for cerebellum (C), midbrain, thalamus, striatum, mesial temporal region, and cortex were drawn on MR images and pasted to corresponding SPECT slices after coregistration. Specific uptake ratios (SURs) at pseudoequilibrium and the simplified reference tissue model (SRTM) methods were used for quantification. SURs were obtained as ([region - C]/C) at each time point. Test-retest variability and reliability (intraclass correlation coefficient [ICC]) were calculated. RESULTS: The highest (123)I-ADAM specific uptake was found in the midbrain and thalamus, followed by the striatum and mesial temporal region. Quantification results using SUR and SRTM were correlated with R = 0.93 (test) and R = 0.94 (retest). SURs remained stable in all regions from 4 to 6 h after injection. Using SUR, test-retest variability/ICC were 13% +/- 11%/0.74 in midbrain, 16% +/- 13%/0.63 in thalamus, 19% +/- 18%/0.62 in striatum, and 22% +/- 19%/0.05 in mesial temporal region. CONCLUSION: (123)I-ADAM accumulates in cerebral regions with high known SERT density. The optimal imaging time for (123)I-ADAM SPECT quantification is suggested to be from 4 to 6 h after a single injection. Long-term test-retest variability and reliability found in the midbrain are comparable to that reported with other (123)I-labeled SPECT ligands. These results support the use of (123)I-ADAM SPECT for SERT imaging after a single injection in humans.     

Altered serotonin transporter availability in patients with multiple sclerosis

Purpose

Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET.

Methods

Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [¹¹C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability.

Results

Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r?=?0.56 vs. BDI, p?=?0.02; r?=?0.49 vs. WEIMuS, p?=?0.05).

Conclusion

Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS.     

Imaging serotonin and dopamine transporters with 123I-beta-CIT SPECT: binding kinetics and effects of normal aging.

[123I]beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (CIT) is a useful ligand for dopamine transporters (DATs) and serotonin transporters (5-HTTs). Previous SPECT studies have shown a state of sustained equilibrium in the striatum on day 2 after injection that allows quantification of striatal DATs using a simple ratio of specific-to-nondisplaceable binding. The aim of this study was to investigate the kinetics of [123I]beta-CIT uptake in the thalamus, hypothalamus, and midbrain, areas known to contain 5-HTTs in high densities. METHODS: SPECT with a triple-head camera was performed on 16 healthy volunteers (13 women, 3 men; mean age [+/-SD], 32 +/- 11 y) after intravenous bolus injection of 130 +/- 20 MBq (3.5 +/- 0.5 mCi) [123I]beta-CIT. Two individuals were scanned 1, 2, 4, 7, 10, 13, 16, and 24 h after injection, and the remaining 14 were scanned 4, 7, 10, 20, and 24 h after injection. Values from 19 previously examined healthy volunteers (8 women, 11 men; mean age, 52 +/- 20 y) were included in the analysis to study the age dependency of beta-CIT binding in striatal and 5-HTT-rich brain areas in a larger control sample. RESULTS: Peak uptake 4 h after injection, followed by stable uptake until 10 h and a slow decrease until 24 h, was observed in the thalamus-hypothalamus region. Activity in the midbrain-pons region peaked 2 h after injection. Because of a concomitant slow but steady decline of uptake in reference regions starting 4 h after injection, a higher stability of binding ratios for 5-HTT-rich brain areas was observed on day 2, suggesting that a state of transient equilibrium is reached between 20 and 24 h but that conditions are only close to transient equilibrium between 4 and 10 h after injection for 5-HTT-rich brain areas. In addition to an age-related decline of striatal [123I]beta-CIT binding of 6.6% per decade, a significant age-associated decrease of beta-CIT binding of 3-4% per decade was found in 5-HTT-rich brain areas. The decline of beta-CIT binding in these regions may be explained, at least in part, by a loss of monoamine transporters with age but may also be related to age-associated morphologic changes. CONCLUSION: [123I]beta-CIT appears to be a suitable ligand for imaging serotonin transporters with SPECT. However, careful age matching is warranted for [123I]beta-CIT SPECT studies of 5-HTT changes in patients with neuropsychiatric disorders.     

In vivo evaluation of [123I]mZIENT as a SPECT radioligand for the serotonin transporter

IntroductionIn vivo imaging of the serotonin transporter continues to be a valuable tool in drug development and in monitoring diseases that alter serotonergic function. The purposes of this study were to: 1) evaluate the test/retest reproducibility of [¹²³I] 2β-Carbomethoxy-3β-(3′-((Z)-2-iodoethenyl)phenyl)nortropane ([¹²³I]mZIENT); and 2) to assess displacement of [¹²³I]mZIENT following administration of SERT specific drugs.MethodsSix female baboons (Papio anubis) were scanned following i.v. administration of [¹²³I]mZIENT. The regional binding potential (BP_nd) was determined using a simplified reference tissue model, with the cerebellum used as a reference region. The test/retest reproducibility of BP_nd was determined following repeated injection of [¹²³I]mZIENT on a different day. To assess the displacement of [¹²³I]mZIENT from SERT, citalopram (0.01–5 mg/kg) or sertraline (0.01–0.5 mg/kg) was given as iv bolus at ~ 4 h following administration of [¹²³I]mZIENT.ResultsThe test/retest variability of BP_nd was less than 10% for all SERT-rich brain regions. Estimates of ED50 for displacement of [¹²³I]mZIENT in SERT-rich regions were consistent with previous reports for the [¹¹C] analog of [¹²³I]mZIENT. Both citalopram and sertraline displaced [¹²³I]mZIENT from SERT in a dose-dependent manner, with maximal observed displacements of greater than 80% in the diencephalon and greater than 75% in brainstem for both citalopram and sertraline.Conclusions[¹²³I] mZIENT demonstrates good test–retest reproducibility; and initial displacement studies suggest that this compound is highly selective for SERT. Overall, this radioligand has favorable characteristics for use in drug development studies and/or longitudinal studies interrogating SERT.     

Imaging of brain tumors with L-3-[123I]iodo-alpha-methyl tyrosine and SPECT

Carbon-11-labeled amino acids have been successfully used to image brain tumors by PET. This study was undertaken to evaluate the potential of L-3-[123I]-iodo-alpha-methyl tyrosine (123IMT) for metabolic imaging of brain tumors. Ten patients (glioblastoma, oligodendroglioma, lymphoma, and metastases) had early and delayed brain SPECT with a rotating gamma camera after i.v.-injection of 200-300 MBq 123IMT. In nine patients the tumors showed intense uptake of the radiotracer. Tumor-to-brain tissue ratios were between 1.4 and 2.6. 123IMT shows potentials for monitoring the effects of brain tumor therapy.     

123I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study.

The serotonergic system may play an important role in the pathophysiology of major depressive disorder (MDD). Few imaging studies have examined serotonin transporter (SERT) binding in patients with MDD. We hypothesized that SERT binding activity may be altered in patients with MDD. This study compared SERT binding in patients with MDD with that in healthy controls. METHODS: We studied SERT activity in 7 patients (22-50 y old) with moderate to severe MDD and 6 healthy controls (24-56 y old) using (123)I-labeled 2-((2-((dimethylamino)methyl) phenyl)thio)-5-iodophenylamine (ADAM) and SPECT brain imaging. Subjects underwent SPECT 4 h after intravenous administration of 185 MBq (5 mCi) of (123)I-ADAM. Images were reconstructed in the axial plane, and region-of-interest demarcations were placed on the midbrain, medial temporal region, and basal ganglia region. RESULTS: (123)I-ADAM binding to SERT in the midbrain was significantly lower (P = 0.01) in MDD patients (1.81 +/- 0.07) than in controls (1.95 +/- 0.13). Age-adjusted (123)I-ADAM binding in the midbrain correlated significantly with scores on the Hamilton Depression Rating Scale (r = 0.82; P = 0.02). A significant negative correlation was observed between (123)I-ADAM SERT binding in the midbrain and age in the healthy control group (r = 0.98; P = 0.0002). SERT binding in the basal ganglia or medial temporal regions of interest did not significantly differ between groups. CONCLUSION: The findings from this preliminary study suggest the possibility of decreased SERT binding in the midbrain region of patients with MDD, with the degree of decrease correlating with the severity of depressive symptoms. There also appears to be an age-related decline in midbrain (123)I-ADAM SERT binding in healthy subjects.     

Compartment analysis of 123I-IMP brain SPECT

To clarify the kinetics of N-isopropyl [123I]p-iodoamphetamine (IMP) in the brain, 2-compartment analysis was applied for brain SPECT with 57-minute dynamic scan in 9 subjects. The model consisted of blood component and brain tissue component. Two transfer rate constants were defined; k1 showed the rate from the blood to the brain tissue, and k2 was that of back diffusion. The late scan was performed 210 minutes after the tracer injection. Suitable k values best fitting to the dynamic data were determined for all regions of interest. Predicted regional cerebral activity at 210 minutes using 57-minute dynamic data was well agreed with measured activity. These showed the kinetics of IMP in the brain was well described by the 2-compartment model. The partition coefficient (k1/k2 ratio) was as large as about 35, and almost constant in the various brain structures including hypoperfused areas. These findings indicated that the initial IMP images reflected the reasonable CBF distribution, which gave relatively reliable CBF values even if using microsphere model.     

Brain SPECT imaging and whole-body biodistribution with [(123)I]ADAM - a serotonin transporter radiotracer in healthy human subjects

INTRODUCTION: [(123)I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([(123)I]ADAM), a novel radiotracer, has promising application in the imaging of the serotonin transporter (SERT) in the human brain. In this study, the optimal scanning time for acquiring brain single photon emission computed tomography (SPECT) images was determined by performing dynamic SPECT studies at intervals from 0 to 6 h postinjection of [(123)I]ADAM. Additionally, radiation-absorbed doses were determined for three healthy human subjects using attenuation-corrected images. METHODS: Twelve subjects were randomized into one of three study groups as follows: whole-body distribution imaging (n=3), dynamic SPECT imaging (n=3) and brain SPECT imaging (n=6). The radiation-absorbed dose was calculated using MIRDOSE 3.0 software with attenuation-corrected data. The specific binding (SB) ratio of the brain stem was measured from dynamic SPECT images to determine the optimal scanning time. RESULTS: Dynamic SPECT images showed that the SB of the brain stem gradually increased to a maximum 4 h postinjection. Single photon emission computed tomography images at 4 h postinjection showed a high uptake of the radiotracer (SB) in the hypothalamus (1.40+/-0.12), brain stem (1.44+/-0.16), pons (1.13+/-0.14) and medial temporal lobe (0.59+/-0.10). The mean adult male value of effective dose was 3.37 x 10(-2) mSv/MBq with a 4.8-h urine-voiding interval. Initial high uptake in SERT-rich sites was demonstrated in the lung and brain. A prominent washout of the radiotracer from the lung further increased brain radioactivity that reached a peak value of 5.03% of injected dose 40 min postinjection. CONCLUSIONS: [(123)I]ADAM is a promising radiotracer for SPECT imaging of SERT in humans with acceptable dosimetry and high uptake in SERT-rich regions. Brain SPECT images taken within 4 h following injection show optimal levels of radiotracer uptake in known SERT sites. However, dynamic changes in lung SERT distribution must be carefully evaluated.     

Clinical significance of I-123 IMP brain SPECT in children with brain diseases

Single photon emission computed tomography (SPECT) of the brain using N-isopropyl p-I-123-iodoamphetamine (I-123 IMP) was performed in 43 children with suspected brain diseases. Forty-three children (25 males and 18 females), with an age range of 24 days-15 years (mean: 6.6 years), were included in the study. Six patients were subsequently diagnosed as normal. Early SPECT of the brain was performed 30 minutes after intravenous administration of 74-111 MBq (2-3 mCi) I-123 IMP using a rotating gamma camera equipped with a 30-degree slant hole and medium energy collimator. Transverse images were reconstructed by Shepp-Logan filtered back projection method with attenuation correction after spatial filtering using an 8th order Butterworth-Wiener filter. Findings of I-123 IMP SPECT were compared with those of X-ray computed tomography (CT) and electroencephalography (EEG). The results showed that 1) In I-123 IMP SPECT, abnormality was found in 30 out of 37 children with brain diseases. The incidence of abnormal findings in the 37 patients was 81% in I-123 IMP SPECT, 61% in X-ray CT, and 78% in EEG., 2) In both cryptogenic and secondary epilepsy, the incidence of abnormality was higher in I-123 IMP SPECT than in X-ray CT. (70% and 94% vs 50% and 81% respectively). Epileptic foci detected by EEG did not correspond with defects found using I-123 IMP SPECT in 27% of the patients., 3) In asphyxiated infants, a high incidence of abnormality was observed on both I-123 IMP SPECT (86%) and X-ray CT (86%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved mapping and quantification of serotonin transporter availability in the human brainstem with the HRRT

Purpose

The serotonin system is involved in many physiological functions and clinical conditions. Serotonergic neurons originate from the raphe nuclei in the brainstem, and reliable estimates of receptor/transporter availability in the raphe in vivo are thus of interest. Though positron emission tomography (PET) can be used to quantify receptor distribution in the brain, high noise levels prevent reliable estimation of radioligand binding in small regions such as the raphe. For this purpose, parametric imaging in combination with high-resolution PET systems may provide images with reduced noise levels and sufficient contrast for reliable quantification. This study examined the potential to evaluate radioligand binding in brainstem nuclei, and assessed the effect of improved resolution on the outcome measures.

Methods

For comparative purposes, radioligand binding was measured with an ECAT EXACT HR PET system (resolution about 4.5 mm FWHM) and a high-resolution research tomograph (HRRT) system (resolution about 1.5 mm FWHM). Six subjects were examined with both systems on the same day using the serotonin transporter radioligand [¹¹C]MADAM. Parametric images of binding potential (BP _ND) were obtained using a wavelet-aided approach. Regions of interest (ROIs) were delineated using a threshold-based semiautomatic delineation procedure for five brainstem structures. Regional BP _ND values were estimated by applying the ROIs to the parametric images, and the percentage difference in BP _ND between the systems was calculated.

Results

Signals for [¹¹C]MADAM binding were obtained for all five brainstem structures. Overall, the HRRT provided 30–40 % higher BP _ND values than the HR (p?=?0.0017), independent of thresholds used in the ROI delineation procedure.

Conclusion

The methodology used enabled the estimation of [¹¹C]MADAM binding in the small nuclei of the brainstem. Differences in the BP _ND values calculated using data from the two systems were mainly attributable to their differing resolutions. The estimated BP _ND values provided lower across-subject variability than those previously obtained using compartment analysis. This procedure may therefore facilitate quantitative studies of receptor/transporter availability in the brainstem.