Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.     

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and ¹²³I-IBZM SPET for the in vivo imaging of dopamine D₂ receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of ¹²³I-epidepride, but only one showed specific binding of ¹²³I-IBZM. Specific binding of ¹²³I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of ¹²³I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of ¹²³I-epidepride in the pituitary region was consistently higher than that of ¹²³I-IBZM. None of the patients who showed absence of uptake of ¹²³I-epidepride in the pituitary area showed uptake of ¹²³I-IBZM in this area. In conclusion: ¹²³I-epidepride SPET is superior to ¹²³I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, ¹²³I-epidepride should replace ¹²³I-IBZM for future D₂ receptor SPET studies of pituitary adenomas. ¹²³I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy. Received 11 July and in revised form 25 September 1998     

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D₂ receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [¹²³I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D₂ receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=–0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D₂ receptors with SPET using [¹²³I]epidepride. Received 6 September and in revised form 21 October 1999     

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with123I-BMIPP and201TI

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method JEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included.²⁰¹T1 cross-talk into the¹²³I acquisition window (group 1,n = 30) and¹²³I cross-talk into the²⁰¹Tl window (group 2,n = 41) were studied. In group 1,¹²³I images were first obtained (single-isotope images), followed by²⁰¹Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual¹²³I-BMIPP/²⁰¹Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.     

Single-photon emission tomography imaging of serotonin transporters in the non-human primate brain with the selective radioligand [123I]IDAM

A new radioligand, 5-iodo-2-[[2–2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol ([¹²³I]IDAM), has been developed for selective single-photon emission tomography (SPET) imaging of SERT. In vitro binding studies suggest a high selectivity of IDAM for SERT (K _i=0.097 nM), with considerably lower affinities for norepinephrine and dopamine transporters (NET K _i= 234 nM and DAT K _i>10 μM, respectively). In this study the biodistribution of SERT in the baboon brain was investigated in vivo using [¹²³I]IDAM and SPET imaging. Dynamic sequences of SPET scans were performed on three female baboons (Papio anubis) after injection of 555 MBq of [¹²³I]IDAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 90–120 min after injection of [¹²³I]IDAM. Similar studies were performed using a NET inhibitor, nisoxetine, and a DAT blocker, methylphenidate. After 60–120 min, the regional distribution of tracer within the brain reflected the characteristic distribution of SERT, with the highest uptake in the midbrain area (hypothalamus, raphe nucleus, substantia nigra), and the lowest uptake in the cerebellum (an area presumed free of SERT). Peak specific binding in the midbrain occurred at 120 min, with a ratio to the cerebellum of 1.80±0.13. At 30 min, 85% of the radioactivity in the blood was metabolite. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited rapid washout from areas with high concentrations of SERT (dissociation rate constant in the midbrain, averaged over three baboons, k _off=0.025±0.002 min^–1), while the cerebellar activity distribution was undisturbed (washout rate 0.0059± 0.0003 min^–1). Calculation of tracer washout rate pixel-by-pixel enabled the generation of parametric images of the dissociation rate constant. Similar studies using nisoxetine and methylphenidate had no effect on the distribution of [¹²³I]IDAM in the brain. These results suggest that [¹²³I]IDAM is suitable for selective SPET imaging of SERT in the primate brain, with high contrast, favorable kinetics, and negligible binding to either NET or DAT. Received: 1 February and in revised form 2 March 1999     

Effect of scatter correction on the compartmental measurement of striatal and extrastriatal dopamine D<Subscript>2</Subscript> receptors using [<Superscript>123</Superscript>I]epidepride SPET

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D₂ receptors using [¹²³I]epidepride. Eight healthy human subjects [age 30±8 (range 22–46) years] participated in a study with a bolus injection of 373±12 (354–389) MBq [¹²³I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry (SC) and without scatter correction using broad-beam (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1–1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [¹⁸F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.     

Cerebellar vascular response to acetazolamide in crossed cerebellar diaschisis: a comparison of99mTc-HMPAO single-photon emission tomography with15O-H2O positron emission tomography

Various observations on the cerebellar vasoreactivity in crossed cerebellar diaschisis (CCD) have previously been reported. The purpose of this study is to clarify the difference between oxygen-15 H₂O positon emission tomographic (PET) and technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomograph (SPET) findings in CCD and to evaluate the effect of the absolute values of the cerebellar blood flow as measured by¹⁵O-H₂O PET on the^99mTc-HMPAO SPET findings. The subjects comprised 15 patients with a supratentorial infarct and CCD. The cerebellar blood flow increased by about 40% at 5 and 20 min after acetazolamide i.v. on both the CCD and the non-CCD side, as measured by 150-1120 PET. The percentage differences in cerebellar blood flow between the CCD and the non-CCD side were –22.3%±5.7% in the resting state, –19.6%±6.4% at 5 min after acetazolamide i.v. and 21.5%±6.7% at 20 min after acetazolamide i.v., as measured by¹⁵O-H₂O PET, while they were –10.6%±5.5% in the resting state and –5.6%±5.1% at 5 min after acetazolamide i.v., as measured by^99mTc-HMPAO SPET. After Lassen's linearization correction, the latter two measurements were –16.2%±7.7% and –9.6%±8.9%, respectively. The effect of acetazolamide did not differ between the CCD and the non-CCD side in¹⁵O–H₂O PET, while a greater response on the CCD side was observed in^99mTc-HMPAO SPET, even after Lassen's linearization correction. It is concluded that acetazolamide HMPAO SPET may overestimate the cerebellar vascular response on the CCD side (or underestimate it on the non-CCD side).     

Iodine-123 labeled nor-β-CIT as a potential tracer for serotonin transporter imaging in the human brain with single-photon emission tomography

Iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl) (nor-β-CIT) is an analogue of β-CIT, which has high affinity to the serotonin transporter. Initial single-photon emission tomography (SPET) studies with [¹²³I]nor-β-CIT were performed in five healthy volunteers. In addition, its metabolism in plasma was investigated with gradient high performance liquid chromatography. [¹²³I]nor-β-CIT was prepared by a method which gave a specific radioactivity of more than 180 GBq/μmol. Unchanged [¹²³I]nor-β-CIT in plasma accounted for 43% and 19% of total radioactivity after 30 and 180 min, respectively. The dynamic SPET studies demonstrated a high and rapid uptake of radioactivity in the brain (6%/ID at 30 min). Highest accumulation was observed in the striatum, the mid-brain and the thalamus. The specific binding in the mid-brain was 33% higher compared with that of [¹²³I]β-CIT. The high radioactivity in the mid-brain is assumed to represent the accumulation of [¹²³I]nor-β-CIT in the serotonin transporter-rich regions, which indicates that [¹²³I]nor-β-CIT might be a potential tracer for visualization of serotonin transporter sites in the human brain with SPET. Received 23 May and in revised form 2 September 1997     

Transmission scanning in emission tomography

Attenuation correction in single-photon (SPET) and positron emission (PET) tomography is now accepted as a vital component for the production of artefact-free, quantitative data. The most accurate attenuation correction methods are based on measured transmission scans acquired before, during, or after the emission scan. Alternative methods use segmented images, assumed attenuation coefficients or consistency criteria to compensate for photon attenuation in reconstructed images. This review examines the methods of acquiring transmission scans in both SPET and PET and the manner in which these data are used. While attenuation correction gives an exact correction in PET, as opposed to an approximate one in SPET, the magnitude of the correction factors required in PET is far greater than in SPET. Transmission scans also have a number of other potential applications in emission tomography apart from attenuation correction, such as scatter correction, inter-study spatial co-registration and alignment, and motion detection and correction. The ability to acquire high-quality transmission data in a practical clinical protocol is now an essential part of the practice of nuclear medicine. Received: 19 February 1998 / Accepted: 19 March 1998     

Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D₂ receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D₂ receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD.The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0.002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0.001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D₂ receptor density can be detected with ¹²³I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD. Received 1 May and in revised form 29 June 1999     

Simultaneous acquisition of iodine-123 emission and technetium-99m transmission data for quantitative brain single-photon emission tomographic imaging

The aim of this study was to obtain quantitative iodine-123 brain single-photon emission tomographic (SPET) images with scatter and attenuation correction. We used a triple-headed SPET gamma camera system equipped with fan-beam collimators with a technetium-99m line transmission source placed at one of the focal lines of the fan-beam collimators. Four energy windows were employed for data acquisition: (a) 126–132 keV, (b) 132–143 keV, (c) 143–175 keV and (d) 175–186 keV. A simultaneous transmission-emission computed tomography scan (TCT-ECT) was carried out for a brain phantom containing ¹²³I solution. The triple energy window scatter correction was applied to the ¹²³I ECT data measured by means of the windows (b), (c) and (d) acquired by two detectors. Attenuation maps were reconstructed from ^99mTc TCT data measured by means of the windows (a), (b) and (c) acquired by one detector. Chang’s iterative attenuation correction method using the attenuation maps was applied to the ¹²³I ECT images. In the phantom study cross-calibrated SPET values obtained with the simultaneous mode were almost equal to those obtained with the sequential mode, and they were close to the true value, within an error range of 5.5%. In the human study corrected images showed a higher grey-to-white matter count ratio and relatively higher uptake in the cerebellum, basal ganglia and thalamus than uncorrected images. We conclude that this correction method provides improved quantification and quality of SPET images and that the method is clinically practical because it requires only a single scan with a ^99mTc external source. Received 6 June and in revised form 27 July 1998     

Single-photon emission tomography imaging of serotonin transporters in the nonhuman primate brain with [123I]ODAM

We have described previously a selective serotonin transporter (SERT) radioligand, [¹²³I]IDAM. We now report a similarly potent, but more stable IDAM derivative, 5-iodo-2-[2-[(dimethylamino)methyl]phenoxy]benzyl alcohol ([¹²³I]ODAM). The imaging characteristics of this radioligand were studied and compared against [¹²³I]IDAM. Dynamic sequences of single-photon emission tomography (SPET) scans were obtained on three female baboons after injection of 375 MBq of [¹²³I]ODAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 120 min after injection of [¹²³I]ODAM. Total integrated brain uptake of [¹²³I]ODAM was about 30% higher than [¹²³I]IDAM. After 60–120 min, the regional distribution of tracer within the brain reflected the characteristic distribution of SERT. Peak specific binding in the midbrain occurred 120 min after injection, with an equilibrium midbrain to cerebellar ratio of 1.50±0.08, which was slightly lower than the value for [¹²³I]IDAM (1.80± 0.13). Both the binding kinetics and the metabolism of [¹²³I]ODAM were slower than those of [¹²³I]IDAM. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited washout from areas with high concentrations of SERT, with a dissociation kinetic rate constant k _off=0.0085±0.0028 min^–1 in the midbrain. Similar studies using nisoxetine and methylphenidate showed no displacement, consistent with its low binding affinity to norepinephrine and dopamine transporters, respectively. These results suggest that [¹²³I]ODAM is suitable for selective SPET imaging of SERT in the primate brain, with higher uptake and slower kinetics and metabolism than [¹²³I]IDAM, but also a slightly lower selectivity for SERT. Received 1 May and in revised form 31 May 1999     

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. Received 3 August and in revised form 1 October 1997     

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D2 receptors with SPET using [123I]epidepride.     

Single-photon emission tomography imaging of serotonin transporters in the non-human primate brain with the selective radioligand [(123)I]IDAM.

A new radioligand, 5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol ([(123)I]IDAM), has been developed for selective single-photon emission tomography (SPET) imaging of SERT. In vitro binding studies suggest a high selectivity of IDAM for SERT (K(i)=0.097 nM), with considerably lower affinities for norepinephrine and dopamine transporters (NET K(i)= 234 nM and DAT K(i)>10 microM, respectively). In this study the biodistribution of SERT in the baboon brain was investigated in vivo using [(123)I]IDAM and SPET imaging. Dynamic sequences of SPET scans were performed on three female baboons (Papio anubis) after injection of 555 MBq of [(123)I]IDAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 90-120 min after injection of [(123)I]IDAM. Similar studies were performed using a NET inhibitor, nisoxetine, and a DAT blocker, methylphenidate. After 60-120 min, the regional distribution of tracer within the brain reflected the characteristic distribution of SERT, with the highest uptake in the midbrain area (hypothalamus, raphe nucleus, substantia nigra), and the lowest uptake in the cerebellum (an area presumed free of SERT). Peak specific binding in the midbrain occurred at 120 min, with a ratio to the cerebellum of 1.80+/-0.13. At 30 min, 85% of the radioactivity in the blood was metabolite. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited rapid washout from areas with high concentrations of SERT (dissociation rate constant in the midbrain, averaged over three baboons, k(off)=0. 025+/-0.002 min(-1)), while the cerebellar activity distribution was undisturbed (washout rate 0.0059+/- 0.0003 min(-1)). Calculation of tracer washout rate pixel-by-pixel enabled the generation of parametric images of the dissociation rate constant. Similar studies using nisoxetine and methylphenidate had no effect on the distribution of [(123)I]IDAM in the brain. These results suggest that [(123)I]IDAM is suitable for selective SPET imaging of SERT in the primate brain, with high contrast, favorable kinetics, and negligible binding to either NET or DAT.     

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [¹²³I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [¹²³I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology. Received 2 October and in revised form 29 December 1997     

Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([¹²³I]IBZM), a D₂ receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [¹²³I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [¹²³I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: –1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [¹²³I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.     

Evaluation of 75Br-labelled butyrophenone neuroleptics for imaging cerebral dopaminergic receptor areas using positron emission tomography

A comparative evaluation of three radiobrominated butyrophenone neuroleptics — bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP) — was made to assess the applicability of these compounds as radiopharmaceuticals labelled with the positron emitter ⁷⁵Br (T _1/2=1.6 h) for mapping cerebral dopaminergic receptor areas non-invasively with positron emission tomography (PET). BSP, BBP, and BP were prepared in high specific activities with high radiochemical yields, using electrophilic reactions with no-carrier-added ⁷⁷Br^- or ⁷⁵Br^-. Screening tests in rats using ⁷⁷Br-labelled compounds indicated D₂-specific localization for ⁷⁷Br-BSP and ⁷⁷Br-BBP, whereas PET experiments in baboons showed that only ⁷⁵Br-BSP preferentially localized in cerebral tissues rich in dopaminergic receptors. The data suggest an inverse relationship between cerebral uptake and receptor-specific localization, which was attributed to a complicated interplay between the D₂ receptor binding affinity, lipophilicity, % ionization and molecular weight of the radioligand, and the binding capacity of the cerebral tissues. ⁷⁵Br-BSP gave a striatumto-cerebellum ratio of 3 in baboon brain 5 h post-injection, which allowed visualization of dopaminergic-receptor-containing areas of the living brain using PET.     

Complementarity of magnetic resonance spectroscopy,positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission

The three techniques allowing the noninvasive study of cardiac metabolism, namely magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPET), all use external detection with stable or radioactive isotopes. These techniques yield different information. PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism (oxygen consumption, glucose and fatty acid utilization) to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high (hydrogen 1, phosphorus 31, fluorine 19 ...) or low (carbon 13, Deuterium) natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques (measurement of the volume, measurement of the quantity of each molecule, resolution, partial volume effect, improvement of the signal-to-noise ratio, movement of the organ). The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by³¹P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and¹³C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with¹⁸F-fluorodeoxyglucose (¹⁸FDG) can determine the glucose consumption and¹H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with¹¹C for PET or¹³C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyopathies, but some initial results using³¹P-MRS are being obtained.     

Automatic segmentation of dynamic neuroreceptor single-photon emission tomography images using fuzzy clustering

The segmentation of medical images is one of the most important steps in the analysis and quantification of imaging data. However, partial volume artefacts make accurate tissue boundary definition difficult, particularly for images with lower resolution commonly used in nuclear medicine. In single-photon emission tomography (SPET) neuroreceptor studies, areas of specific binding are usually delineated by manually drawing regions of interest (ROIs), a time-consuming and subjective process. This paper applies the technique of fuzzy c-means clustering (FCM) to automatically segment dynamic neuroreceptor SPET images. Fuzzy clustering was tested using a realistic, computer-generated, dynamic SPET phantom derived from segmenting an MR image of an anthropomorphic brain phantom. Also, the utility of applying FCM to real clinical data was assessed by comparison against conventional ROI analysis of iodine-123 iodobenzamide (IBZM) binding to dopamine D₂/D₃ receptors in the brains of humans. In addition, a further test of the methodology was assessed by applying FCM segmentation to [¹²³I]IDAM images (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio] benzyl alcohol) of serotonin transporters in non-human primates. In the simulated dynamic SPET phantom, over a wide range of counts and ratios of specific binding to background, FCM correlated very strongly with the true counts (correlation coefficient r ²>0.99, P<0.0001). Similarly, FCM gave segmentation of the [¹²³I]IBZM data comparable with manual ROI analysis, with the binding ratios derived from both methods significantly correlated (r ²=0.83, P<0.0001). Fuzzy clustering is a powerful tool for the automatic, unsupervised segmentation of dynamic neuroreceptor SPET images. Where other automated techniques fail completely, and manual ROI definition would be highly subjective, FCM is capable of segmenting noisy images in a robust and repeatable manner. Received 16 November 1998 and in revised form 20 January 1999