The effect of morphine on regional cerebral blood flow measured by 99mTc-ECD SPECT in dogs.

To gain insights into the working mechanism of morphine, regional cerebral blood flow (rCBF) patterns after morphine administration were assessed in dogs. In a randomized cross-over experimental study, rCBF was estimated with 99mTc-Ethylcysteinate Dimer single photon emission computed tomography in 8 dogs at baseline, at 30 minutes and at 120 minutes after a single bolus of morphine. Perfusion indices (PI) in the frontal, parietal, temporal and occipital cortex and in the subcortical and cerebellar region were calculated. PI was significantly decreased 30 min after morphine compared to baseline in the right frontal cortex. The left parietal cortex and subcortical region showed a significantly increased PI 30 min after morphine compared to baseline. No significant differences were noted for the other regions or at other time points. In conclusion, a single bolus of morphine generated a changing rCBF pattern at different time points.

The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT.

Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.

Regional brain perfusion changes during standard and microburst vagus nerve stimulation in dogs.

PURPOSE: Vagus nerve stimulation (VNS) is an effective adjunctive treatment for refractory epilepsy in humans, but its mechanism of action (MOA) and optimal stimulation parameters are still unknown. Functional neuroimaging studies could provide better insight into the brain structures involved in the activity of VNS, but have not yet been described in dogs. The aim of this study was to investigate the effect of acute VNS on the regional cerebral blood flow (rCBF) in dogs using micro-SPECT (µ-SPECT). Additionally, a novel stimulation paradigm (microburst VNS) was used and compared with standard VNS. METHODS: A VNS Therapy System was implanted in ten Beagle dogs. µ-SPECT was performed after sham, standard and microburst VNS in a randomized, cross-over study. Nineteen volumes of interest (VOIs) were semi-quantitatively analysed and perfusion indices (PIs) were calculated. Furthermore, a rostro-caudal gradient (R-C), an asymmetry index (AI) and a cortical-subcortical index (Co-SCo) were determined. The SPECT results after standard and microburst VNS were compared pairwise with sham stimulation. RESULTS: Acute standard VNS did not cause significant rCBF alterations. Acute microburst VNS caused a significant hypoperfusion in the left frontal lobe (P=0.023) and in the right parietal lobe (P=0.035). Both stimulation paradigms did not cause changes in R-C, AI nor Co-SCo. CONCLUSIONS: Microburst VNS is more potent than standard VNS to modulate the rCBF in the dog. Our results promote further research towards the antiepileptic effect of microburst VNS in dogs and humans.

5-HT2A receptors in the feline brain: 123I-5-I-R91150 kinetics and the influence of ketamine measured with micro-SPECT.

UNLABELLED: Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. METHODS: This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. RESULTS: The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046). CONCLUSION: This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and (123)I-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.

Regional brain perfusion in 12 cats measured with technetium-99m-ethyl cysteinate dimer pinhole single photon emission computed tomography (SPECT).

With the use of perfusion tracers, in vivo examination of the regional cerebral blood flow in cats can be performed with single photon emission computed tomography (SPECT). Reliable perfusion data of normal, healthy cats are necessary for future clinical studies or other research use. Therefore, this dataset of the regional perfusion pattern of the normal feline brain was created. Twelve cats were used in this study. Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) was injected intravenously and the acquisition, using a triple head gamma camera equipped with three multi-pinhole collimators (pinhole SPECT), was started 40 mins after tracer administration under general anaesthesia. Nineteen regions of interest were defined using 7T magnetic resonance images of the feline brain and a topographical atlas. Regional counts were normalised to the counts of two reference regions: the total brain and the cerebellum. The highest tracer uptake was noticed in the subcortical structures, and the lowest in the frontal cortex and the cerebellum. Also left-right asymmetry in the temporal cortex and a rostrocaudal gradient of 5% were observed.

The influence of morphine on cerebral 5-HT2A availability in dogs: a SPECT study.

UNLABELLED: The opioid and serotonergic systems are closely involved in pain processing and mood disorders. The aim of this study was to assess the influence of systemic morphine on cerebral serotonin 2A receptor (5-HT(2A)) binding in dogs using SPECT with the 5-HT(2A) radioligand (123)I-5I-R91150. METHODS: 5-HT(2A) binding was estimated with and without morphine pretreatment in 8 dogs. The 5-HT(2A) binding indices in the frontal, parietal, temporal, and occipital cortex and in the subcortical region were obtained by semiquantification. RESULTS: A significantly decreased 5-HT(2A) binding index was found in the morphine group for the right (morphine, 1.41 ± 0.06; control, 1.52 ± 0.10) and left (morphine, 1.44 ± 0.08; control, 1.55 ± 0.11) frontal cortices, with P = 0.012 and P = 0.040, respectively. No significant differences were noted for the other regions. CONCLUSION: Morphine decreased the frontocortical 5-HT(2A) availability, confirming an interaction between the 5-HTergic and the opioid systems. Whether this interaction is caused by decreased receptor density due to direct internalization or is the result of indirect actions, such as increased endogenous serotonin release, remains to be elucidated.

99mTc-labeled tricarbonyl his-CNA35 as an imaging agent for the detection of tumor vasculature.

UNLABELLED: Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. METHODS: (99m)Tc-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. (99m)Tc-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. RESULTS: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. (99m)Tc-(CO)(3) His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of (99m)Tc-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. CONCLUSION: (99m)Tc-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.

Serotonin 2A receptor, serotonin transporter and dopamine transporter alterations in dogs with compulsive behaviour as a promising model for human obsessive-compulsive disorder.

Neuro-imaging studies have shown altered, yet often inconsistent, serotonergic and dopaminergic neurotransmission in patients with obsessive-compulsive disorder (OCD). We investigated both serotonergic and dopaminergic neurotransmission in 9 drug-naïve dogs with compulsive behaviour, as a potential model for human OCD. Single photon emission computed tomography was used with (123)I-R91150 and (123)I-FP-CIT, in combination with (99m)Tc-ECD brain perfusion co-registration, to measure the serotonin (5-HT) 2A receptor, dopamine transporter (DAT) and serotonin transporter (SERT) availability. Fifteen normally behaving dogs were used as reference group. Significantly lower 5-HT2A receptor radioligand availability in frontal and temporal cortices (bilateral) was observed. Further, in 78% of the compulsive dogs abnormal DAT ratios in left and right striatum were demonstrated. Interestingly, both increased and decreased DAT ratios were observed. Finally, significantly lower subcortical perfusion and (hypo)thalamic SERT availability were observed in the compulsive dogs. This study provides evidence for imbalanced serotonergic and dopaminergic pathways in the pathophysiology of compulsions in dogs. The similarities with the altered neurotransmission in human OCD provide construct validity for this non-induced, natural canine model, suggesting its usefulness for future investigations of the pathophysiology of human OCD as well as the effectiveness of psychopharmacological interventions.

Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging.

BACKGROUND: For any new vaginal dosage form, the distribution and retention in the vagina has to be assessed by in vivo evaluation. We evaluated the vaginal distribution and retention of starch-based pellets in sheep as live animal model by gamma scintigraphy (using Indium-111 DTPA as radiolabel) and in women via magnetic resonance imaging (MRI, using a gadolinium chelate as contrast agent). A conventional cream formulation was used as reference in both studies. METHOD: Cream and pellets were administered to sheep (n=6) in a two period-two treatment study and to healthy female volunteers (n=6) via a randomized crossover trial. Pellets (filled into hard gelatin capsule) and cetomacrogol cream, both labeled with Indium-111 DTPA (for gamma scintigraphy) or with gadolinium chelate (for MRI) were evaluated for their intravaginal distribution and retention over a 24h period. Spreading in the vagina was assessed based on the part of the vagina covered with formulation (expressed in relation to the total vaginal length). Vaginal retention of the formulation was quantified based on the radioactivity remaining in the vaginal area (sheep study), or qualitatively evaluated (women study). RESULTS: Both trials indicated a rapid distribution of the cream within the vagina as complete coverage of the vaginal mucosa was seen 1h after dose administration. Clearance of the cream was rapid: about 10% activity remained in the vaginal area of the sheep 12h post-administration, while after 8h only a thin layer of cream was detected on the vaginal mucosa of women. After disintegration of the hard gelatin capsule, the pellet formulation gradually distributed over the entire vaginal mucosa. Residence time of the pellets in the vagina was longer compared to the semi-solid formulation: after 24h 23 ± 7% radioactivity was detected in the vaginal area of the sheep, while in women the pellet formulation was still detected throughout the vagina. CONCLUSION: A multi-particulate system containing starch-based pellets was identified as a promising novel vaginal drug delivery system, resulting in complete coverage of the vaginal mucosa and long retention time.

(99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values.

In this study we investigated the influence of technical factors (positioning, background (BG) correction and attenuation correction) on qualitative and quantitative (absolute (AU) and relative (RU) uptake) assessment of feline kidneys with (99m)technetium labelled dimercaptosuccinic acid ((99m)Tc-DMSA). Eleven healthy adult cats were included. Influence of BG and depth correction on quantitative assessment was evaluated. Depth correction was based on the geometric mean method (using dorsal and ventral images) and the use of two standards placed over each individual kidney. Visual evaluation showed superiority of dorsal and ventral over lateral positioning due to increased separation of the kidneys permitting region of interest (ROI) placement without overlap. No apparent influence of BG correction was found for RU. However, AU was systematically overestimated without BG correction. Depth correction did not seem to affect RU in most cases, however, in some cats the differences were not negligible. The values for AU without depth correction were lower compared to depth corrected values.

Desirability function combining metabolic stability and functionality of peptides.

The evaluation of peptides as potential therapeutic or diagnostic agents requires the consideration of several criteria that are targeted around two axes: functionality and metabolic stability. Most often, a compromise has to be made between these mutually opposing characteristics. In this study, Derringer's desirability function, a multi-criteria decision-making method, was applied to determine the best peptide for opioid studies in a single figure-of-merit. The penetration of the blood-brain barrier (BBB) determines the biological functionality of neuropeptides in the brain target tissue, and consists of an influx and an efflux component. The metabolic stability in the two concerned tissues, i.e. plasma and brain, are taken into consideration as well. The overall selection of the peptide drug candidate having the highest BBB-drugability is difficult due to these conflicting responses as well as the different scalings of the four biological parameters under consideration. The highest desirability, representing the best BBB-drugability, was observed for dermorphin. This peptide is thus the most promising drug candidate from the set of eight opioid peptides that were investigated. The least desirable candidate, with the worst BBB influx and/or metabolic stability, was found to be CTAP. Validation of the desirability function by in vivo medical imaging showed that dermorphin and DAMGO penetrate the BBB, whereas EM-1 and TAPP did not. These results are thus consistent with those obtained with the desirability evaluation. To conclude, the multi-criteria decision method was proven to be useful in biomedical research, where a selection of the best candidate based on opposing characteristics is often required.

Single photon emission computed tomography (SPECT) imaging of the dopamine transporter in healthy dogs.

Single photon emission computed tomography (SPECT) with the cocaine-analogue [(123)I]-FP-CIT is widely used for in vivo assessment of the dopamine transporter (DAT) availability. Dopaminergic disturbance has been implicated in neurological and behavioural disorders in humans and animals. Ten healthy dogs were scanned at three different time points (between 3 h and 6 h post-tracer injection) under general anaesthesia (1.4% isoflurane). A pseudo-equilibral state was reached 3-6 h after tracer injection with normal reference values for the DAT binding indices (mean±SD) of 15.39±2.38 (left) and 15.23±2.23 (right). By determining the pseudo-equilibrium and the normal DAT binding indices of normally behaving dogs, this study paves the way for future research on the relationship between abnormal canine behaviour and a disturbed dopaminergic system.

Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders.

The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders. Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical (123)I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious. Significantly (P<0.0056) altered 5-HT 2A receptor binding indices were found in bilateral frontal, temporal and occipital cortical brain areas of the dogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ≥1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ≤1.73 with 86.4% sensitivity and 18.2% (1-specificity). We conclude that SPECT imaging with the radioligand (123)I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.

Transrectal ultrasonography of the left adrenal gland in healthy horses.

Little information is available on medical imaging of the adrenal glands in horses. We investigated the feasibility of transrectal ultrasonography to characterize the normal equine adrenal gland. Transrectal ultrasonography was performed in 25 healthy horses using a 7.5 MHz linear array probe at a displayed depth of 8 cm. Transrectal ultrasonography of the right adrenal gland was not feasible. For the left adrenal gland, the left kidney, the abdominal aorta, the left renal artery, the left renal vein, and the cranial mesenteric artery were used as landmarks. The size of the left adrenal gland was variable, but it generally appeared as a long, flat structure with a hyperechoic medulla surrounded by a hypoechoic cortex. The most cranial part of the gland could not be delineated appropriately in 11 horses (44%). The mean (+/-SD) thickness of the gland and medulla was 0.66 +/- 0.15cm (n = 25) and 0.28 +/- 0.09 cm (n = 25) near the caudal pole, 0.87 +/- 0.25 cm (n = 14) and 0.40 +/- 0.18 cm (n = 12) near the cranial pole, and 0.89 +/- 0.18 cm (n = 25) and 0.36 +/- 0.13 cm (n = 25) in the middle of the gland, respectively. The mean (+/-SD) length of the entire adrenal gland and of the medulla was 6.22 +/- 0.77 cm (n = 14) and 5.45 +/- 0.71 cm (n = 6), respectively. Transrectal ultrasonography allowed adequate visualization of the left adrenal gland in horses.

Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies.

Regional brain perfusion in epileptic dogs evaluated by technetium-99m-ethyl cysteinate dimer SPECT.

We evaluated the feasibility of interictal single photon emission computed tomography (SPECT) to detect alterations in regional cerebral blood flow and neuronal activity in dogs with idiopathic epilepsy. Twelve dogs with idiopathic epilepsy underwent interictal technetium-99m-ethyl cysteinate dimer SPECT of the brain. Different cortical regions of interest (ROIs), 1 ROI at the cerebellum and 1 ROI at the subcortical area were evaluated by semiquantitative analysis and compared with a control group (18 dogs). Significant hypoperfusion (P = 0.02) was present in the subcortical area of epileptic dogs. This hypoperfusion was not associated with seizure frequency, age at onset of seizures, duration of epilepsy, or time since the last seizure. Interictal SPECT did not reveal cortical or cerebellar perfusion alterations. The subcortical area may play an important role in the pathophysiology of canine idiopathic epilepsy.

Evaluation of the brain 5-HT2A receptor binding index in dogs with anxiety disorders, measured with 123I-5I-R91150 and SPECT.

UNLABELLED: The serotonergic system has been implicated in emotional and cognitive functions since early work. In particular, an important role has been attributed to the 5-HT2A receptor in schizophrenia, depression, eating disorders, and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT2A receptor in dogs with severe anxiety disorder, using 123I-5I-R91150 and SPECT. METHODS: SPECT was performed with the 5-HT2A receptor-specific radioligand 123I-5I-R91150 to determine the 5-HT2A receptor binding index (BI) in the brains of dogs. Sixteen dogs with pathologic anxiety problems were compared with 22 normal-behaving reference dogs. RESULTS: Lower 5-HT2A receptor BI was found in the left (P=0.001) and right (P=0.002) frontal cortices in the group of dogs with anxiety disorders than in the reference group. Right (P=0.022) and left (P=0.048) temporocortical BIs were also significantly lower in the dogs with anxiety disorders. Finally, the BI was significantly lower in the right occipital cortex (P=0.038) of dogs with anxiety disorders than in the reference dogs. After correction for multiple comparisons (P<0.0056), only the bilateral frontocortical lower BI remained significant. CONCLUSION: The findings in this study indicate that the 5-HT2A receptor is involved in the pathophysiology of anxiety disorders in dogs. The affected brain regions are in concordance with the brain regions involved in human anxiety disorders. The acquired data confirm the potential of using the dog as a natural model for investigation of the different mechanisms of anxiety disorders. In this regard, the use of dogs may contribute to the development of novel treatment approaches and new drugs for veterinary and human use.

Evaluation of serotonin-2A receptor occupancy with 123I-5-I-R91150 and single-photon emission tomography before and after low-dose pipamperone administration in the canine brain.

PURPOSE: To conduct a cost-efficient pilot study on the effect of low-dose pipamperone on the serotonin-2A receptor binding in a large animal model with conventional single-photon emission tomography modalities. METHODS: Three healthy drug-naive female Beagle dogs were scanned before and after administration of a single-dose pipamperone of 5 and 10 mg. Acquisition was performed under general anesthesia 90 min after injection of the specific radioligand 123I-5-I-R91150 with a triple head gamma-camera (Triad, Trionix). Binding index and receptor occupancy were calculated on the emission data after image fusion with the emission data from the individual 99mTc-ethyl cysteinate dimer perfusion scans to optimize frontal cortex delineation. RESULTS: A dose-dependent reduction of the binding index was observed after single low-dose pipamperone, suggestive for competition of this cold compound with the radioligand for the 5-HT2A receptor. The calculated mean-binding serotonin-2A binding index in the frontal cortex was 1.47 before treatment and reduced to 1.28 after one dose of pipamperone 5 mg and to 1.08 after one dose of pipamperone 10 mg. The calculated occupancy was 40.4% after one dose of 5 mg pipamperone and 83% after one dose of 10 mg pipamperone. CONCLUSION: This experiment supports the hypothesis that pipamperone, even in the low-dose range, significantly blocks serotonin-2A receptors. This study also demonstrates the value of the canine model to investigate the effects of drugs on neurotransmitter systems. Repeated nuclear imaging brain scanning experiments with different paradigms and medication doses are possible with conventional imaging equipment in a well-accepted laboratory species.

Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat.

Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT(4)) and for the thyroid to salivary gland ratio with sodium pertechnetate gamma-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT(4) and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.