In vivo quantification of the [(11)C]DASB binding in the normal canine brain using positron emission tomography.

BACKGROUND: [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) is currently the mostly used radiotracer for positron emission tomography (PET) quantitative studies of the serotonin transporter (SERT) in the human brain but has never been validated in dogs. The first objective was therefore to evaluate normal [(11)C]DASB distribution in different brain regions of healthy dogs using PET. The second objective was to provide less invasive and more convenient alternative methods to the arterial sampling-based kinetic analysis. RESULTS: A dynamic acquisition of the brain was performed during 90 min. The PET images were coregistered with the magnetic resonance images taken prior to the study in order to manually drawn 20 regions of interest (ROIs). The highest radioactivity concentration of [(11)C]DASB was observed in the hypothalamus, raphe nuclei and thalamus and lowest levels in the parietal cortex, occipital cortex and cerebellum. The regional radioactivity in those 20 ROIs was quantified using the multilinear reference tissue model 2 (MRTM2) and a semi-quantitative method. The values showed least variability between 40 and 60 min and this time interval was set as the optimal time interval for [(11)C]DASB quantification in the canine brain. The correlation (R(2)) between the MRTM2 and the semi-quantitative method using the data between 40 and 60 min was 99.3% (two-tailed p-value < 0.01). CONCLUSIONS: The reference tissue models and semi-quantitative method provide a more convenient alternative to invasive arterial sampling models in the evaluation of the SERT of the normal canine brain. The optimal time interval for static scanning is set at 40 to 60 min after tracer injection.

Effect of recombinant human thyroid stimulating hormone on radioactive iodine uptake by thyroid carcinoma in dogs.

BACKGROUND: The high doses of radioiodine-131 (131I) and, subsequently, the high radioactive burden for dog and environment warrants optimization of 131I therapy in dogs with thyroid carcinoma (TC). HYPOTHESIS/OBJECTIVES: To evaluate the effect of a revised protocol with recombinant human thyroid stimulating hormone (rhTSH) on tumor radioactive iodine uptake (RAIU) in dogs with TC. ANIMALS: Nine client-owned dogs diagnosed with TC. METHODS: A prospective cross-over study in which tumor RAIU was calculated and compared at 8 hours (8h-RAIU) and 24 hours (24h-RAIU) after injection of radioactive iodine-123 (123I), once with and once without rhTSH (ie, 250 µg, IM, 24 and 12 hours before 123I) in each dog. Simultaneously, serum total thyroxine (TT4) and TSH were measured at baseline (T0), and 6 (T6), 12 (T12), 24 (T24), and 48 hours (T48) after the first rhTSH administration. RESULTS: Tumor RAIU was significantly higher at 24 hours with rhTSH compared to no rhTSH (mean difference = 8.85%, 95% CI of [1.56; 16.14]; P = .03), while this was non-significant at 8 hours (mean difference = 4.54%, 95% CI of [0.35; 8.73]; P = .05). A significant change of serum TT4 (median difference T24 - T0 = 35.86 nmol/L, interquartile range [IQR] = 15.74 nmol/L) and TSH (median difference T24 - T0 = 1.20 ng/mL, IQR = 1.55 ng/mL) concentrations occurred after administration of rhTSH (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Recombinant human TSH could optimize 131I treatment in dogs with TC by increasing tumor RAIU and thus 131I treatment efficacy.

Normal regional distribution of cerebral blood flow in dogs: comparison between (99m) Tc-ethylcysteinate dimer and (99m) Tc- hexamethylpropylene amine oxime single photon emission computed tomography.

Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.

Radioiodine treatment in hyperthyroid cats: insights into the characteristics of owners and their cats, and owner motivation and perceptions.

OBJECTIVES: Radioiodine (131I) therapy is the most appropriate treatment option for many hyperthyroid cats, as it is minimally invasive and often curative. Nevertheless, 131I treatment is not always pursued by owners. Hence, it is important to obtain more insight into owner satisfaction during and after 131I treatment, and their decision-making process. In this study, we describe the characteristics of owners and their hyperthyroid cats referred for 131I therapy, and determine owners' motivation and how they experienced the 131I treatment of their cat. METHODS: A survey was sent to owners whose cats underwent 131I therapy (n = 1071) between 2010 and 2017 at Ghent University. The survey contained 35 questions with tick-box or free-text answer options concerning family situation, pet insurance, previous therapy, comorbidities, motivation for 131I therapy and owner perception of this treatment. RESULTS: In total, 438 owners completed 94% or more of the questionnaire. Over half of the cats (55%) had received previous medical, dietary or surgical treatment. Motivations for changing the initial therapy to 131I therapy included difficulties in administering medication (31%), insufficient improvement in clinical signs (23%), side effects (16%) and following the referring veterinarian's advice (16%). Almost a fifth of owners (18%) were not informed about the existence of 131I therapy by their veterinarian and found information on 131I treatment online or through friends. Hospitalising their cat was very distressing for 17% of owners. Most owners (92%) were satisfied with the treatment. Reasons for dissatisfaction were insufficient communication, iatrogenic hypothyroidism, persistent hyperthyroidism and comorbidities post-treatment. CONCLUSIONS AND RELEVANCE: Our study stresses the importance of communication regarding the possible outcome of 131I treatment, the importance of managing underlying comorbidities before treatment and anticipating the stress of owners during their cat's hospitalisation period. The results of this study could help in improving client communication when advising on 131I treatment.

Ultrasound-guided core needle biopsy in dogs with thyroid carcinoma.

Currently, a histological diagnosis of highly vascularized canine (c) thyroid carcinoma (TC) is primarily obtained following excisional biopsy (EB) through thyroidectomy. Non-EBs are contraindicated in unresectable invasive cTCs due to their highly vascularized nature, which subsequently, lack histological diagnosis. We hypothesised ultrasound-guided core needle biopsy (UGCNB) to be a safe biopsy technique to obtain an accurate histological diagnosis in unresectable TCs. Nine client-owned dogs with suspected naturally occurring TC, presented for surgical excision, were included. First, a UGCNB was taken from the cervical tumour, followed by EB. Haemorrhage following UGCNB was evaluated preoperatively and once the tumour was surgically exposed by visual inspection and ultrasonography. Histological analysis, including cell organisation, tumour capsular and vascular invasion, and immunohistochemistry were performed and compared between both biopsy specimens (i.e., UGCNB and EB) of the same dog. Pre- and peroperative visual inspection revealed minor, localised haemorrhage, subsequent to the UGCNB, in 7/9 dogs. Histology of the EBs confirmed TC in 8/9 dogs and was inconclusive in 1/9 dogs. Histology of the UGCNBs revealed neoplastic thyroid tissue in 7/9 UGCNBs and was inconclusive in 1/9 UGCNBs. The remaining UGCNB contained no mass related tissue and was, therefore, excluded. Histological parameters (i.e., cell organisation, tumour capsular and vascular invasion) were not concordant between 6/8 included UGCNBs and their respective EB. Immunolabelling for thyroglobulin and calcitonin was concordant between all eight included UGCNBs and their respective EB. The remaining evaluated immunohistochemical markers (i.e., cyclooxygenase-2 [COX-2], P-glycoprotein and vascular endothelial growth factor [VEGF]) were concordant between the included UGCNBs and the EBs in 6/8 dogs. To conclude, UGCNBs can be safely obtained in suspected cTCs and enable a reliable diagnosis of the thyroid origin, thyroid cell origin and potential therapeutic markers such as COX-2, P-glycoprotein and VEGF. Subsequently, UGCNB enables clinicians to establish an individually tailored treatment plan in dogs with unresectable TC.

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.

Evaluation of serum lidocaine/monoethylglycylxylidide concentration to assess shunt closure in dogs with extrahepatic portosystemic shunts.

BACKGROUND: Liver function tests do not always normalize despite successful attenuation of extrahepatic portosystemic shunts (EHPSS). OBJECTIVES: Assess the lidocaine/monoethylglycylxylidide (MEGX) test to determine liver perfusion after EHPSS closure. ANIMALS: Twenty dogs with EHPSS. METHODS: A prospective cohort study was performed and all dogs were tested at diagnosis, 1, 3, and 6 months postoperatively. After collecting a baseline blood sample (T0), 1 mg/kg body weight of lidocaine was injected intravenously. Fifteen (T15) and 30 minutes (T30) later, blood was collected. Plasma concentrations of lidocaine and its metabolites MEGX and glycylxylidide (GX) were determined, using a high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method. Three months postoperatively, transsplenic portal scintigraphy was performed to determine EHPSS closure. RESULTS: At T15, median MEGX concentrations were higher in dogs with closed EHPSS compared to diagnosis (33.73 ng/mL [21.11-66.44 ng/mL] vs 13.74 ng/mL [7.25-21.93 ng/mL]; P < .001), but were not different (12.28 ng/mL [10.62-23.17 ng/mL] vs 13.74 ng/mL [7.25-21.93 ng/mL]) in dogs with persistent shunting. Sensitivity to determine shunt closure for MEGX at T15 was 96.2% (95% confidence interval [CI]: 78.4-99.8) and specificity 82.8% (95% CI: 63.5-93.5). CONCLUSIONS AND CLINICAL IMPORTANCE: The lidocaine/MEGX test is a promising, rapid, and noninvasive blood test that seems helpful to differentiate dogs with closed EHPSS and dogs with persistent shunting after gradual attenuation.

Liver-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin in cats with chronic kidney disease and hyperthyroidism.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. OBJECTIVE: To evaluate urinary and serum L-FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (131 I) treatment. ANIMALS: Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131 I treatment. METHODS: Cross-sectional and longitudinal study. Serum L-FABP (sL-FABP), serum NGAL (sNGAL), urinary L-FABP (uL-FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min-max). RESULTS: CKD cats had significantly higher sL-FABP (13.50 [3.40-75.60] ng/ml) and uL-FABP/Cr (4.90 [0.97-2139.44] µg/g) than healthy cats (4.25 [1.34-23.25] ng/ml; P = .01 and 0.46 [0.18-9.13] µg/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL-FABP/Cr (0.94 [0.15-896.00] µg/g) than healthy cats (P < .001), thereafter uL-FABP/Cr significantly decreased at T2 (0.54 [0.10-76.41] µg/g, P = .002). For the detection of CKD, uL-FABP/Cr had 100% (95% confidence interval [CI], 66.4-100.0) sensitivity and 93.2% (95% CI, 81.3-98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: L-FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL-FABP to predict azotemia after treatment in hyperthyroid cats remains unknown.

Comparison of free thyroxine measurement by chemiluminescence and equilibrium dialysis following 131I therapy in hyperthyroid cats.

OBJECTIVES: The first objective was to assess correlation between free thyroxine (fT4) measurements by equilibrium dialysis (fT4ED; Antech Diagnostics) and a chemiluminescent enzyme immunoassay (fT4CEIA; IMMULITE 2000 Veterinary Free T4 [Siemens Healthcare Diagnostics Products]) in hyperthyroid, otherwise healthy, cats before (T0), and 1 month (T1) and 11-23 months (T2) after radioactive iodine (131I) therapy. The second objective was to determine correlation between thyroid status based on fT4 (by both techniques) and the gold standard, thyroid scintigraphy. METHODS: Thyroid status, including thyroid-stimulating hormone (TSH), total thyroxine (TT4) and fT4 serum concentrations, were assessed in 45 client-owned hyperthyroid cats before (T0), and 1 month (T1) and 11-23 months (T2) after 131I therapy. fT4 was determined by a chemiluminescent enzyme immunoassay (CEIA) and equilibrium dialysis (ED). Quantitative thyroid scintigraphy (with sodium 99m-Tc-pertechnetate) was performed at T2. RESULTS: Spearman correlation between fT4CEIA and fT4ED was 0.81, 0.88 and 0.79 at T0, T1 and T2, respectively. fT4CEIA was consistently lower than fT4ED, with a median difference of -5.4 pmol/l (P <0.001) and -4.9 pmol/l (P <0.0001) at T1 and T2, respectively. At T2, all cats were identified as euthyroid based on thyroid scintigraphy. None of the cats were identified as being hypothyroid, based on serum TT4 and TSH measurements. Nine of 22 (40.9%) cats had an fT4CEIA below the reference interval (RI) at T2, whereas only 2/22 (9.1%) cats had an fT4ED concentration below the RI at T2. CONCLUSIONS AND RELEVANCE: Good correlation exists between both assays at T1 and T2, but a significant systematic difference is noted at both time points. This could be an indication for reconsideration of the current RI, although further studies are warranted for assessing test accuracy (in otherwise healthy cats and cats with non-thyroidal illness). At this time, routine use of fT4CEIA after 131I therapy is not advised in feline patients.

Diagnostic value of blood variables following attenuation of congenital extrahepatic portosystemic shunt in dogs.

BACKGROUND: The aims of this study were to determine if extrahepatic portosystemic shunt (EHPSS) postoperative closure could be predicted based on preoperative blood analyses and to determine the accuracy of blood variables to evaluate persistence of portosystemic shunting postoperatively (multiple acquired portosystemic shunts (MAPSS) or persistent EHPSS). METHODS: Retrospectively, 62 dogs treated surgically for congenital EHPSS that underwent postoperative trans-splenic portal scintigraphy or CT angiography three to six months postoperatively were included. RESULTS: None of the studied preoperative blood variables could unambiguously predict surgical outcome. Elevated postoperative fasting venous ammonia (FA) concentration always indicated surgical failure (persistent shunting or MAPSS), but normal FA did not provide any information on the postoperative shunting status. Paired serum bile acids (SBA) were not reliable enough to confirm or exclude postoperative shunting. In the presence of low normal postoperative FA levels, elevated preprandial SBA was more likely in dogs with persistent shunting (sensitivity of 0.79, specificity of 0.83), whereas postprandial SBA below reference limit was more often observed in case of surgical success (sensitivity of 0.93, specificity of 0.67). CONCLUSION: Blood variables, and more specifically the combination of FA and SBA, are not a valuable alternative to advanced medical imaging to reliably assess the surgical outcome after EHPSS surgery.

Planar and single-photon emission computed tomography imaging in dogs with thyroid tumors: 68 cases.

BACKGROUND: Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease. HYPOTHESIS/OBJECTIVES: To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection. ANIMALS: Sixty-eight dogs with thyroid neoplasia. METHODS: Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018). RESULTS: Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia.

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats.

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Assessment of symmetric dimethylarginine as a biomarker of renal function in hyperthyroid cats treated with radioiodine.

BACKGROUND: Measurement of serum creatinine (sCr) and urea nitrogen fail to detect decreased renal function in many hyperthyroid cats because of low muscle mass and glomerular hyperfiltration of affected cats. Serum symmetric dimethylarginine (sSDMA) is an earlier and more sensitive renal biomarker than sCr. OBJECTIVE: Evaluate sSDMA as a biomarker of renal function in hyperthyroid cats before (T0) and 1 month after (T1) radioiodine (131 I) treatment. ANIMALS: Forty-seven client-owned hyperthyroid nonazotemic cats were evaluated at T0 and T1. METHODS: A prospective study in which sCr and sSDMA concentrations were determined in 47 hyperthyroid cats at T0 and at T1. Glomerular filtration rate (GFR) was estimated at T0 and T1 in 10 of these 47 cats using plasma exogenous creatinine clearance test. RESULTS: Serum SDMA was elevated (>14 µg/dL) in 6 of 47 cats at T0 and normalized after treatment in 4 of those cats. All cats remained nonazotemic after treatment. In 10 cats in which GFR was measured, correlation between GFR and sSDMA was low and not significant (τb = -0.35, P = .17 at T0 and τb = -.22, P = .41 at T1), whereas correlation between GFR and sCr was moderate and significant (τb = -0.52, P < .05 at T0 and τb = -.53, P = <.05 at T1). CONCLUSIONS AND CLINICAL IMPORTANCE: Careful interpretation of mildly increased sSDMA with normal sCr in hyperthyroid cats is warranted as sSDMA values might normalize after resolution of hyperthyroidism in some cats. In this population of hyperthyroid cats, sSDMA was poorly correlated with GFR.

Assessment of pharmacologically induced changes in canine kidney function by multiparametric magnetic resonance imaging and contrast enhanced ultrasound.

Introduction: Dynamic contrast-enhanced (DCE) MRI and arterial spin labeling (ASL) MRI enable non-invasive measurement of renal blood flow (RBF), whereas blood oxygenation level-dependent (BOLD) MRI enables non-invasive measurement of the apparent relaxation rate (R2*), an indicator of oxygenation. This study was conducted to evaluate the potential role of these MRI modalities in assessing RBF and oxygenation in dogs. The correlation between contrast-enhanced ultrasound (CEUS) and the MRI modalities was examined and also the ability of the MRI modalities to detect pharmacologically induced changes. Methods: RBF, using CEUS, ASL- and DCE-MRI, as well as renal oxygenation, using BOLD-MRI of eight adult beagles were assessed at two time-points, 2­3 weeks apart. During each time point, the anesthetized dogs received either a control (0.9% sodium chloride) or a dopamine treatment. For each time point, measurements were carried out over 2 days. An MRI scan at 3 T was performed on day one, followed by CEUS on day two. Results: Using the model-free model with caudal placement of the arterial input function (AIF) region of interest (ROI) in the aorta, the DCE results showed a significant correlation with ASL measured RBF and detected significant changes in blood flow during dopamine infusion. Additionally, R2* negatively correlated with ASL measured RBF at the cortex and medulla, as well as with medullary wash-in rate (WiR) and peak intensity (PI). ASL measured RBF, in its turn, showed a positive correlation with cortical WiR, PI, area under the curve (AUC) and fall time (FT), and with medullary WiR and PI, but a negative correlation with medullary rise time (RT). During dopamine infusion, BOLD-MRI observed a significant decrease in R2* at the medulla and entire kidney, while ASL-MRI demonstrated a significant increase in RBF at the cortex, medulla and the entire kidney. Conclusion: ASL- and BOLD-MRI can measure pharmacologically induced changes in renal blood flow and renal oxygenation in dogs and might allow detection of changes that cannot be observed with CEUS. However, further research is needed to confirm the potential of ASL- and BOLD-MRI in dogs and to clarify which analysis method is most suitable for DCE-MRI in dogs.

LC-UV/MS characterization and DOE optimization of the iodinated peptide obestatin.

The aim of this study was to investigate the direct iodination of the recently discovered peptide obestatin by LC-UV/ESI ion trap MS analysis. The influence of selected reaction parameters on obestatin iodination by chloramine-T, Iodo-Gen((R)) and lactoperoxidase was investigated by experimental design. Different responses, i.e. species percentage and yield, peptide recovery and iodination yield were evaluated. Mono-up till tetra-iodinated species are possible depending on the reaction conditions with electrophilic substitutions occurring at Tyr(16) and His(19) as confirmed by LC/MS/MS. The two possible mono-iodinated obestatin isomers, i.e. [I(1)-Tyr(16)]-obestatin and [I(1)-His(19)]-obestatin, could be chromatographically separated. Several significant main and quadratic effects, and interaction of factors were observed from which optimum conditions for a specific response could be derived. The highest impact on the response surface diagrams was overall attributed to the amount of iodide added. Synthesis methods were compared relative to the different response factors: lactoperoxidase was found to be the overall most robust iodination technique, and also gave the highest mono-iodinated species yield. The applicability of our research was demonstrated by non-carrier-added (125)I-radioiodination. To our knowledge, this is the first time an LC separation of mono-iodinated peptide isomers has been reported.

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.

Predictive value of scintigraphic (semi-)quantitative thyroid parameters on radioiodine therapy outcome in hyperthyroid cats.

Objectives The outcome of radioiodine therapy in hyperthyroid cats is suspected to be influenced by multiple factors. The degree of activity of the thyroid gland, represented by uptake of sodium pertechnetate or tracer activities of radioiodine by the thyroid gland on thyroid scintigraphy, has been suggested in the literature as one of those. Thyroid gland pertechnetate uptake can be represented by (semi-)quantitative factors such as the thyroid to salivary gland (T/S) ratio, the thyroid to background (T/B) ratio and the percentage technetium uptake by the thyroid glands (%TcU). The aim of this study was to investigate a possible relationship between these thyroid scan parameters and radioiodine therapy outcome. Methods Sodium pertechnetate thyroid scans of 75 hyperthyroid cats were retrospectively evaluated and statistical analysis was performed with and without correction for injected radioiodine activity. Three different background regions of interest (ROIs) were used to calculate the T/B ratio and %TcU: 'neck', 'circle' and 'copy ROI'. Results Higher T/S ratios were found to be significantly related to a persistent hyperthyroid outcome in both analyses. For the T/S ratio, a threshold value of 5.4 was determined, with a sensitivity of 73% and a specificity of 59%. An increased risk for persistent hyperthyroidism compared with a final euthyroid outcome with an increased T/Bcircle ratio was only found to be significant without correction for the activity of radioiodine administered. For the %TcU no statistical significance was reached. Regarding a low total thyroxine outcome, no significant relationships with any of the investigated parameters were found. Conclusions and relevance The findings of this study suggest that semi-quantification of thyroid gland uptake is best performed using the T/S ratio. A T/S ratio ⩾5.4 is a possible indicator for an increased risk of persistent hyperthyroidism.

Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a 99mtechnetium-hexamethylpropylene amine oxime (99mTc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.

Week-to-week variation of scintigraphic (semi-)quantitative thyroid variables in 14 healthy experimental cats.

Although scintigraphy is an important tool for the assessment of thyroid function in cats, time variation of commonly used thyroid variables has not been investigated to this day. The aim of this study was to investigate whether a week-to-week variation of scintigraphic variables exists in healthy cats of a magnitude that is clinically relevant, as this could lead to misinterpretation of results. Fourteen adult, healthy, experimental cats were included in the study. At 3 time points, with 7-day intervals, the cats underwent a thyroid pertechnetate scan and blood samples were collected. The scintigraphic variables calculated were the thyroid to salivary gland ratio (T/S), thyroid to background ratio (T/B), percentage technetium uptake in the thyroid glands (%TcUT) and additionally percentage technetium uptake in the salivary glands (%TcUSG). Two thyroid hormones, total thyroxine (TT4) and thyroid stimulating hormone (TSH), were included in the analysis. All scintigraphic variables, with the exception of the %TcUT and T/Bneck ratio, were within the normal reference ranges reported in literature. No clinically relevant week-to-week variation was observed for any of the variables included in this study.