PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring: fundamentals,early results and future perspectives

Functional imaging using positron emission tomography (PET) plays an important role in the diagnosis, staging, image‐guided treatment planning and monitoring of malignant diseases. PET imaging complements conventional anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). The strength of CT scanning lies in its high spatial resolution, allowing for anatomical characterization of disease. PET imaging, however, moves beyond anatomy and characterizes tissue based on functions such as metabolic rate. Combined PET/CT scanners were introduced commercially in 2001 and a number of technological advancements have since occurred. Radiolabelled tracers such as ¹⁸F‐fluorodeoxyglucose (FDG) and ¹⁸F‐fluorothymidine (FLT) allow visualization of various metabolic processes within cancer cells. Many studies in human oncology evaluating the utility of PET/CT have demonstrated clinical benefits. Few veterinary studies have been performed, but initial studies show promise for improved detection of malignancy, more thorough staging of canine cancer and determination of early response and disease recrudescence.     

Assessment of the ultrasonographic characteristics of the podotrochlear apparatus in clinically normal horses and horses with navicular syndrome

OBJECTIVE: To characterize the normal ultrasonographic appearance of the podotrochlear apparatus in horses by use of standardized measurements and identify soft tissue changes associated with navicular syndrome. DESIGN: Prospective study. ANIMALS: 7 clinically normal horses and 28 horses with navicular syndrome. PROCEDURE: The feasibility of identifying and measuring the soft tissue structures of the podotrochlear apparatus ultrasonographically via the transcuneal approach was assessed in 2 additional horses without navicular syndrome; both horses were euthanatized, and the structures identified ultrasonographically were confirmed at necropsy. Ultrasonographs were obtained in the study horses. Objective and subjective data were obtained to characterize ultrasonographic changes associated with navicular syndrome. RESULTS: Abnormalities of the flexor surface of the distal sesamoid (navicular) bone, the impar ligament, the distal digital annular ligament, deep digital flexor tendon (DDFT), and the podotrochlear (navicular) bursa were assessed via the transcuneal ultrasonographic approach. No significant differences were found between the measurements of the podotrochlear apparatus in normal horses and those with navicular syndrome; however, important subjective differences were detected ultrasonographically in horses with navicular syndrome. In horses with navicular syndrome, ultrasonographic findings were indicative of navicular bursitis, dystrophic mineralization of the DDFT and impar ligament, tendonitis and insertional tenopathy of the DDFT, desmitis of the impar ligament, and cortical changes in the flexor surface of the navicular bone. CONCLUSIONS AND CLINICAL RELEVANCE: Findings of ultrasonographic evaluation of the hoof appear to be useful in determining the cause of caudal heel pain and characterizing the components of navicular syndrome in horses.     

Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease

ObjectivesTo determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD).Animals22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe).MethodsN-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearman's rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations.ResultsNT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P = 0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P < 0.001) and the NT-CKD (P < 0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P < 0.001) and the NT-CKD (P = 0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration.ConclusionsMeasurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.     

The effects of maternal nutrition during the first 50 d of gestation on the location and abundance of hexose and cationic amino acid transporters in beef heifer uteroplacental tissues

We hypothesized that maternal nutrition during the first 50 d of gestation would influence the abundance of hexose transporters, SLC2A1, SLC2A3, and SLC2A5, and cationic amino acid transporters, SLC7A1 and SLC7A2, in heifer uteroplacental tissues. Angus-cross heifers (n = 43) were estrus synchronized, bred via artificial insemination, and assigned at breeding to 1 of 2 dietary intake groups (CON = 100% of requirements to achieve 0.45 kg/d of BW gain or RES = 60% of CON intake) and ovariohysterectomized on day 16, 34, or 50 of gestation (n = 6 to 9/d) in a completely randomized design with a 2 × 3 factorial arrangement of treatments. Uterine cross-sections were collected from the horn ipsilateral to the corpus luteum, fixed in 10% neutral buffered formalin, sectioned at 5 µm, and stained via immunofluorescence for transporters. For each image, areas of fetal membrane (FM; chorioallantois), luminal epithelium (ENDO), superficial glands (SG), deep glands (DG), and myometrium (MYO) were analyzed separately for relative intensity of fluorescence as an indicator of transporter abundance. Analysis of FM was only conducted for days 34 and 50. No transporters in target areas were influenced by a day × treatment interaction (P ≥ 0.06). In ENDO, all transporters were differentially abundant from days 16 to 50 of gestation (P ≤ 0.04), and SLC7A2 was greater (P = 0.05) for RES vs. CON. In SG, SLC7A1 and SLC7A2 were greater (P ≤ 0.04) at day 34 vs. day 16. In DG, SLC2A3 and SLC7A1 were greater (P ≤ 0.05) for CON vs. RES heifers; furthermore, SLC7A1 was greater (P < 0.01) at day 50 vs. days 16 and 34 of gestation. In MYO, SLC7A1 was greater (P < 0.01) for CON vs. RES and was greater (P = 0.02) at days 34 and 50 vs. day 16. There were no differences in FM (P ≥ 0.06). Analysis of all uterine tissues at day 16 determined that SLC2A1, SLC2A3, and SLC7A2 were all differentially abundant across uterine tissue type (P < 0.01), and SLC7A1 was greater (P = 0.02) for CON vs. RES. Analysis of all uteroplacental tissues at days 34 and 50 demonstrated that all transporters differed (P < 0.01) across uteroplacental tissues, and SLC7A1 was greater (P < 0.01) for CON vs. RES. These data are interpreted to imply that transporters are differentially affected by day of gestation, and that hexose and cationic amino acid transporters are differentially abundant across utero-placental tissue types, and that SLC7A1 is responsive to maternal nutritional treatment.     

Relative bioavailability of organic bis-glycinate bound copper relative to inorganic copper sulfate in beef steers fed a high antagonist growing diet

To assess the relative bioavailability of bis-glycinate bound Cu, 90 Angus-cross steers (265 ± 21 kg) were blocked by body weight (BW) to pens with GrowSafe bunks and randomly assigned to dietary treatments (14 to 18 steers/treatment): 0 mg supplemental Cu/kg dry matter (DM; CON), 5 or 10 mg supplemental Cu/kg DM as Cu sulfate (CS5; CS10) or bis-glycinate bound Cu (GLY5; GLY10). Steers received a high antagonist growing diet (analyzed 4.9 mg Cu/kg DM, 0.48% S, and 5.3 mg Mo/kg DM). Steers were weighed at the beginning (days 1 and 0) and end (days 125 and 126) of the trial to determine average daily gain (ADG) and gain:feed (G:F). Blood was collected from all steers on days 0, 28, 56, 84, and 126. Liver samples were collected on days −3 or −2 and day 123 or 124. Data were analyzed using ProcMixed of SAS (experimental unit = steer; fixed effect = treatment and block). Plasma Cu was analyzed as repeated measures (repeated effect = day). Plasma and liver Cu concentrations were regressed against total Cu intake using ProcGLM to calculate relative bioavailability of GLY. Final BW and overall ADG were greatest for CS5 and CS10 and least for CON and GLY5 (P = 0.01). Overall, DMI was not affected by treatment (P = 0.14), but overall G:F tended to be greatest for CS5, CS10, and GLY5 and least for CON (P = 0.08). Total and supplemental Cu intake was greatest for steers supplemented either source at 10 mg Cu/kg DM and least for CON (P < 0.01). However, total and supplemental Cu intake was greater for CS5 than GLY5 (P < 0.01). Final liver Cu concentrations were greatest for CS10, least for CON, CS5, and CS10, and intermediate for GLY10 (P < 0.01). Final plasma Cu was greatest for steers supplemented either source at 10 mg Cu/kg DM (P < 0.01). Relative bioavailability of GLY was 82% compared to CS based on liver Cu (P < 0.01) but did not differ based on plasma Cu (P = 0.60). The lesser bioavailability of GLY relative to CS could be due to a high concentration of dietary antagonists and lower solubility of GLY (68.9% relative to CS) in pH conditions (5.2) similar to the ruminal pH of a beef animal consuming a high concentrate diet. Future studies should examine the effects of bis-glycinate bound Cu fed in blended combination with inorganic Cu sulfate to determine the most effective blend of sources for feedlot cattle experiencing varying amounts of dietary Cu antagonists.     

Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses

Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg⁻¹ hr⁻¹ for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration–time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (K_e), half-life (t_1/2e), volume of distribution (V_d), and clearance (Cl). Median and range were 0.42 (0.15–0.97)/hr, 1.68 (0.87–4.52) hr, 5.85 (2.10–19.34) L/kg, and 28.7 (19.6–39.5) ml min⁻¹ kg⁻¹, respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (C_max) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.     

Influence of amount and frequency of protein supplementation to ruminants consuming low-quality cool-season forages: efficiency of nitrogen utilization in lambs and performance of gestating beef cows

We evaluated the influence of amount and crude protein (CP) supplementation frequency (SF) on nitrogen (N) use by wethers and the performance of late-gestation beef cows. In exp. 1, seven Western whiteface wethers (31.8 ± 1.4 kg) were used in an incomplete 7 × 4 Latin square to evaluate intake and N use. Wethers received one of the seven treatments in a 2 × 3 factorial design containing two levels of supplemental soybean meal offered at a rate of 100% (F) or 50% (H; 50% of F) of the estimated CP requirement daily, once every 5, or once every 10 d, plus a non-supplemented control (CON). Low-quality cool-season forage (4.9 % CP; dry matter [DM] basis) was provided daily for ad libitum intake. Experimental periods lasted 30 d. In exp. 2, 84 Angus × Hereford cows (560 ± 35 kg) were stratified by age, body condition score (BCS), and expected calving date and allocated to 1 of the 21 feedlot pens (three pens per treatment). Pens were randomly assigned to receive the same treatments as in exp. 1 and cows had free access to low-quality cool-season forage (2.9% CP; DM basis). Cow body weight (BW) and BCS were measured every 14 d until calving and within 24 h after calving. In exp. 1, supplementation did not alter total DM and organic matter (OM) intake (P ≥ 0.26), but both parameters linearly decreased as SF decreased (P = 0.02). Supplementation increased DM, OM, and neutral detergent fiber (NDF) digestibility (P ≤ 0.02). Additionally, F feeding linearly increased DM, OM, and NDF digestibility as SF decreased (P ≤ 0.04). Digestibility of N, N balance, and digested N retained were greater with supplementation (P < 0.01), and N digestibility linearly increased as SF decreased (P = 0.01). Mean plasma urea-N concentration was not only greater (P < 0.01) for supplemented vs. CON wethers but also greater (P = 0.03) for F vs. H. In exp. 2, pre-calving BCS change was greater (P = 0.03) for supplemented cows. A linear effect of SF × supplementation rate for pre-calving BCS change was noted (P = 0.05), as F-supplemented cows lost more BCS compared with H as SF decreased. When considering supplementation intervals greater than 5 d, reducing the quantity of supplement provided, compared with daily supplementation, may be a feasible management strategy to maintain acceptable nutrient use and animal performance while reducing supplement and labor costs.