COMPARISON BETWEEN 2‐18F‐FLUORO‐2‐DEOXY‐D‐GLUCOSE POSITRON EMISSION TOMOGRAPHY AND CONTRAST‐ENHANCED COMPUTED TOMOGRAPHY FOR MEASURING GROSS TUMOR VOLUME IN CATS WITH ORAL SQUAMOUS CELL CARCINOMA

Feline oral squamous cell carcinoma is one of the most refractory feline malignancies. Most patients succumb due to failure in local tumor control. 2‐¹⁸F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (¹⁸F‐FDG PET) is increasingly being used for veterinary oncology staging as it highlights areas with higher glucose metabolism. The goal of the current prospective study was to compare gross tumor volume measurements using ¹⁸F‐FDG PET vs. those using computed tomography (CT) for stereotactic radiation therapy planning in cats with oral squamous cell carcinoma. Twelve cats with confirmed oral squamous cell carcinoma underwent pretreatment ¹⁸F‐FDG PET/CT. Gross tumor volumes based on contrast‐enhanced CT and ¹⁸F‐FDG PET were measured and compared among cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary squamous cell carcinoma group (n = 8, P = 0.002) and for the total number of patients (n = 12, P = 0.006), but not in the lingual/laryngeal group (n = 4, P = 0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high‐¹⁸F‐FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group (P = 0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that ¹⁸F‐FDG PET warrants further investigation as a supplemental imaging modality in cats with oral squamous cell carcinoma because it detected regions of possible primary tumor that were not detected on CT images.     

Relative skeletal distribution of proliferating marrow in the adult dog determined using 3′‐deoxy‐3′‐[18F]fluorothymidine

3′‐deoxy‐3′‐[¹⁸F]fluorothymidine (¹⁸FLT) is a radiopharmaceutical tracer used with positron emission tomography (PET), often in combination with computed tomography (CT), to image DNA synthesis, and thus, cellular proliferation. Characteristic accumulation of the tracer within haematopoietic bone marrow provides a noninvasive means to assess marrow activity and distribution throughout the living animal. The present study utilizes three‐dimensional analysis of ¹⁸FLT‐PET/CT scans to quantify the relative skeletal distribution of active marrow by anatomic site in the dog. Scans were performed on six healthy, adult (3–6 years of age), mixed‐breed dogs using a commercially available PET/CT scanner consisting of a 64‐slice helical CT scanner combined with an integrated four ring, high‐resolution LSO PET scanner. Regions of interest encompassing 11 separate skeletal regions (skull, cervical vertebral column, thoracic vertebral column, lumbar vertebral column, sacrum, ribs, sternum, scapulae, proximal humeri, ossa coxarum, and proximal femora) were manually drawn based on CT images and thresholded by standardized uptake value to delineate bone marrow activity. Activity within each skeletal region was then divided by the total skeletal activity to derive the per cent of overall marrow activity within an individual site. The majority of proliferative marrow was located within the vertebral column. Of the sites traditionally accessed clinically for marrow sampling, the proximal humerus contained the largest percentage, followed by the ossa coxarum, proximal femur, and sternum, respectively. This information may be used to guide selection of traditional marrow sampling sites as well as inform efforts to spare important sites of haematopoiesis in radiation therapy planning.     

Measurements of hypoxia ([18F]‐FMISO, [18F]‐EF5) with positron emission tomography (PET) and perfusion using PET ([15O]‐H2O) and power Doppler ultrasonography in feline fibrosarcomas*

The aim of this study was to evaluate if hypoxia in feline fibrosarcomas can be detected. This was done using positron emission tomography (PET), two hypoxia tracers and polarographic pO₂ measurements. Of the seven cats included, five received [¹⁸F]‐fluoromisonidazole and two 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N‐(2,2,3,3,3‐pentafluoropropyl) acetamide. Perfusion was evaluated with [¹⁵O]‐H₂O (n = 4) and with contrast‐enhanced power Doppler ultrasonography (n = 5). Hypoxia was detected in three cats. Polarographic pO₂ measurements did not confirm PET results. In the ultrasonographic evaluation, low vascularity and low perfusion were seen with a peripheral vascular pattern and no perfusion in the centre of the tumour. This was in contrast to the [¹⁵O]‐H₂O scans, where central perfusion of the tumour was also found. In conclusion, it appears that hypoxia exists in this tumour type. The presence of tumour necrosis and heterogeneous hypoxia patterns in these tumours may explain the found discrepancies between the applied techniques.     

Evaluation of 18F‐FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma

18F‐fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG‐PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy‐proven oral SCC were imaged with whole body 18FDG‐PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG‐PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9–24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG‐PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG‐PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.     

CHARACTERIZATION OF PHYSIOLOGIC 18F‐FDG UPTAKE WITH PET‐CT IN DOGS

We evaluated the whole body distribution of 2‐deoxy‐2‐[18F]fluoro‐d ‐glucose (¹⁸F‐FDG) in seven beagle dogs using positron emission tomography/computed tomography. The mean and maximum standard uptake values (SUV) for various tissues were computed. The SUV of the aortic blood pool was 0.65±0.19. Moderate uptake was present in brain (3.40±1.01). Mild uptake was present in orbital muscles, soft palate, laryngeal and pharyngeal region, mandibular salivary gland, myocardium, liver, pancreas, kidney, and intestine. ¹⁸F‐FDG uptake would be normally higher in these tissues because of normal physiologic activity. Mean and maximum SUV values of the eye, skeletal muscle, bone tissue, spleen, adrenal gland, stomach, tongue, gall bladder, and lung were similar to or lower than that of the aortic blood pool. These data provide a normal baseline for comparing pathologic ¹⁸F‐FDG uptake.     

MEASUREMENT OF BODY COMPOSITION IN CATS USING COMPUTED TOMOGRAPHY AND DUAL ENERGY X‐RAY ABSORPTIOMETRY

Dual energy X‐ray absorptiometry (DEXA) is a reference method for assessing body composition but is seldom `accessible in veterinary settings. Computed tomography (CT) can provide similar body composition estimates and we propose that it can be used in body composition studies in animals. We compared CT and DEXA data from 73 healthy adult neutered domestic cats. Three approaches for measuring adipose tissue percentage from full‐body CT scans were explored. By examining the frequency distribution of voxels by Hounsfield unit (HU) value, it is possible to calculate a fat index (Fat%) that is in close agreement with the fat percentages obtained from DEXA scans. Fat% values obtained by the best of the methods had a mean difference of 0.96% (95% confidence interval 0.33–1.59%) from the DEXA results. Fat% obtained by the other two methods were characterized by good correlation but poor agreement and in one of the methods, the difference between the values from the two modalities was proportional to their mean. By using CT, it is possible to obtain body composition estimates that are in close agreement with those available using DEXA. While the significance of individual Fat% measurements obtained from CT can be difficult to interpret and to compare between centers, CT can contribute to research studies concerned either with nutrition or with obesity‐related disorders.     

NORMAL THORACIC AND ABDOMINAL DISTRIBUTION OF 2-DEOXY-2-[18F]FLUORO-d-GLUCOSE (18FDG) IN ADULT CATS

Positron emission tomography (PET) with 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) is an important imaging modality for diagnosis and staging of human neoplastic disease. The purpose of this study is to describe the normal ¹⁸FDG uptake in adult cats. Six adult healthy female cats were used. Cats were sedated and then injected intravenously with 74.0±13.0 (mean±SD) MBq of ¹⁸FDG. General anesthesia was induced and cats were placed in ventral recumbancy on the PET scanner's bed. Static images using multiple bed positions were acquired approximately 60–90 min after injection. A transmission scan was acquired at each bed position utilizing a ⁵⁷Co point source to perform attenuation and scatter correction. Regions of interest (ROIs) were drawn over the liver, right and left renal cortices, left ventricular wall, and wall of ascending and descending colonic segments. Standardized uptake values (SUV) were calculated using an established formula. Kidneys and intestinal tract had relatively intense uptake of ¹⁸FDG; liver activity was intermediate; the spleen was not identified in any of the cats. Cardiac activity was variable but intense activity was noted in the left ventricular myocardium in most cats. No appreciable lung uptake was noted. Mean±SD SUV values were calculated. This study established the normal pattern of uptake of ¹⁸FDG in adult cats and provided baseline data for comparison with future studies evaluating a variety of neoplastic and nonneoplastic diseases.     

Chronic lymphocytic leukaemia in the cat: 18 cases (2000–2010)

There is little information regarding the presentation, biologic behaviour, treatment and prognosis in cats with chronic lymphocytic leukaemia (CLL), and further investigation is needed to characterize this disease in cats. The goal of this study was to describe the clinical presentation, response to treatment and prognosis of feline CLL. A multi‐institutional retrospective study of 18 cats diagnosed with CLL between 2000 and 2010 was performed. CLL was defined as the presence of a mature lymphocytosis (> 9000 lymphocytes µL^?1) and confirmation of an immunophenotypically monomorphic or clonal lymphoid population. Each patient was required to also have at least one of the two following criteria: (1) concurrent cytopenia of at least one cell line and/or (2) >15% mature lymphocytes in the bone marrow. Data on signalment, history, clinical signs, clinicopathologic features and response to treatment were reviewed. Median age of the cats at initial presentation was 12.5 years (range: 5–20 years). The most common presenting complaint was chronic weight loss, which was present in 8/18 (44%) cats. Sixteen of 18 (89%) cats were treated with chlorambucil and prednisolone; four of these cats also received vincristine. Two (11%) cats were treated with multi‐agent injectable chemotherapy (L‐CHOP, l ‐asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisolone). Eighty‐eight percent of cats evaluable for response achieved a complete (nine cats) or partial (six cats) remission. Median overall remission was 15.7 months (range: 1.3–22.8 months). The median overall survival in the 17 cats with follow‐up data was 14.4 months (range: 0.9–25.3 months). Results of this study suggest that CLL affects older‐aged cats and responds favourably to treatment with oral chlorambucil and prednisolone.     

EFFECTS OF ANESTHETIC PROTOCOL ON NORMAL CANINE BRAIN UPTAKE OF 18F‐FDG ASSESSED BY PET/CT

The purpose of this study was to assess the effects of four anesthetic protocols on normal canine brain uptake of 2‐deoxy‐2‐[¹⁸F]fluoro‐d ‐glucose (FDG) using positron emission tomography/computed tomography (PET/CT). Five clinically normal beagle dogs were anesthetized with (1) propofol/isoflurane, (2) medetomidine/pentobarbital, (3) xylazine/ketamine, and (4) medetomidine/tiletamine–zolazepam in a randomized cross‐over design. The standard uptake value (SUV) of FDG was obtained in the frontal, parietal, temporal and occipital lobes, cerebellum, brainstem and whole brain, and compared within and between anesthetic protocols using the Friedman test with significance set at P<0.05. Significant differences in SUVs were observed in various part of the brain associated with each anesthetic protocol. The SUV for the frontal and occipital lobes was significantly higher than in the brainstem in all dogs. Dogs receiving medetomidine/tiletamine–zolazepam also had significantly higher whole brain SUVs than the propofol/isoflurane group. We concluded that each anesthetic protocol exerted a different regional brain glucose uptake pattern. As a result, when comparing brain glucose uptake using PET/CT, one should consider the effects of anesthetic protocols on different regions of the glucose uptake in the dog's brain.     

USE OF 3'-DEOXY-3'-[18F]FLUOROTHYMIDINE PET/CT FOR EVALUATING RESPONSE TO CYTOTOXIC CHEMOTHERAPY IN DOGS WITH NON-HODGKIN'S LYMPHOMA

Imaging and measurement of proliferation with computed tomography (CT) and positron emission tomography (PET) provide a noninvasive method for improved staging and monitoring of response to cancer treatment. We evaluated prospectively the proliferation marker 3'-deoxy-3'[¹⁸F] fluorothymidine (FLT) in the context of FLT-PET/CT for detection of early response, confirmation of posttreatment response, and prediction of relapse in dogs with non-Hodgkin's lymphoma. Nine dogs with non-Hodgkin's lymphoma who were scheduled to receive five cycles of an investigational cytotoxic chemotherapy agent were included. All dogs received baseline FLT-PET/CT imaging immediately before chemotherapy. Intent was to repeat imaging with FLT-PET/CT at various time points: group 1 ( n =4), 5 days after initiation of chemotherapy and 3 weeks following the last chemotherapy administration; group 2 ( n =5), before the fourth cycle of chemotherapy and 3 weeks following the last administration. Two dogs in group 2 did not undergo repeat PET/CT. Body mass standardized uptake values (SUV) for FLT were calculated for each dog. Eight dogs had initially increased FLT uptake (mean SUV_max=9.8 [2.6–22.3]). Mean SUV decreased significantly for the seven dogs that underwent follow-up PET/CT following chemotherapy (mean SUV_max=3.5 [1.1–7.9], P <0.016). Increased uptake preceded clinical and cytological evidence of relapse in two dogs. Ki-67 immunohistochemistry confirmed decreased proliferation corresponding to decreased SUV in three canine lymph node samples. FLT-PET/CT functional and anatomical imaging shows promise for the evaluation of response to cytotoxic chemotherapy in dogs with non-Hodgkin's lymphoma and for predicting relapse before standard clinical and clinicopathologic confirmation.     

STATIC AND DYNAMIC 18FDG‐PET IN NORMAL HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS)

Positron emission tomography (PET) is often used to stage and monitor human cancer and has recently been used in a similar fashion in veterinary medicine. The most commonly used radiopharmaceutical is 2‐Deoxy‐2‐[¹⁸F]‐Fluoro‐d ‐glucose (¹⁸F‐FDG), which is concentrated and trapped within cells that use glucose as their energy substrate. We characterized the normal distribution of ¹⁸F‐FDG in 10 healthy Hispaniolan Amazon parrots (Amazona ventralis) by performing whole body PET scans at steady state, 60 min after injection. Significant variability was found in the intestinal activity. Avian species are known to reflux fluid and electrolytes from their cloaca into their colon. To evaluate reflux as the cause of variability in intestinal distribution of ¹⁸F‐FDG, dynamic PET scans were performed on the coelomic cavity of six Hispaniolan Amazon parrots from time 0 to 60 min postinjection of radiotracer. Reflux of radioactive material from the cloaca into the colon occurred in all birds to varying degrees and occurred before 60 min. To evaluate the intestinal tract of clinical avian patients, dynamic scans must be performed starting immediately after injection so that increased radioactivity due to metabolism or hypermetabolic lesions such as cancer can be differentiated from increased radioactivity due to reflux of fluid from the cloaca.     

Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk‐3)

Reduced expression in immortalized cells (REIC/Dkk‐3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk‐3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk‐3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk‐3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk‐3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk‐3 represents a potential molecular target for the development of therapies against feline mammary cancers.     

Canine,feline, and equine corneal vascular neoplasia: A retrospective study (2007‐2015)

Corneal vascular neoplasms (hemangioma and hemangiosarcoma) are rare in all species. Reported cases are single case reports in a single species. Archived cases of corneal hemangioma and hemangiosarcoma from dogs, cats, and horses were obtained from the Comparative Ocular Pathology Lab of Wisconsin (COPLOW, Madison, WI), tabulated, and examined. This retrospective study describes the breeds, ages, tumor types, and characteristics of vascular neoplasms that appeared to be primarily corneal in location, in feline, canine, and equine patients, with gross and histologic images. There is a discussion of predisposing factors and speculated association with chronic ocular surface disease.     

EFFECTS OF GADOXETATE DISODIUM (EOVIST®) CONTRAST ON MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF THE LIVER IN CLINICALLY HEALTHY DOGS

Gadoxetate disodium (Gd‐EOB‐DTPA; gadolinium‐ethoxybenzyl‐diethylene triamine penta‐acetic acid) is a newly developed paramagnetic contrast agent reported to have a high specificity for the hepatobiliary system in humans. The purpose of this prospective study was to describe effects of Gd‐EOB‐DTPA contrast administration on MRI characteristics of the liver in eight clinically healthy dogs. Precontrast dorsal and transverse T1‐weighted spin echo, T2‐weighted fast spin echo, and transverse T1‐weighted 3D gradient echo (VIBE; volume‐interpolated body examination) pulse sequences were acquired for each dog. Dogs were assigned to four groups based on contrast dose administered (0.0125 mmol/kg or 0.025 mmol/kg), and pulse sequences acquired after contrast administration (T1‐weighted spin echo and T1‐weighted 3D gradient echo). Liver signal intensity ratios were calculated and compared between the two contrast dose groups and two postcontrast pulse sequence groups using ANOVA. No adverse effects of contrast administration were observed. All dogs exhibited homogeneous contrast enhancement of the liver with no statistical difference in enhancement between the two different contrast doses. Contrast enhancement in all dogs peaked between 1 and 10 min after intravenous injection. There was a significant difference in mean signal intensity ratios between sequences (P = 0.035) but not between doses (P = 0.421). Postcontrast signal intensities of the liver parenchyma were significantly higher for the T1‐weighted 3D gradient echo images when compared to the T1‐weighted spin echo sequences. Findings indicated that Gd‐EOB‐DTPA contrast administration is safe in healthy dogs and causes homogeneous enhancement of the liver that is more pronounced in T1‐weighted 3D gradient echo MRI pulse sequences.     

Treatment of feline mammary tumours using chemotherapy,surgery and a COX‐2 inhibitor drug (meloxicam): a retrospective study of 23 cases (2002–2007)*

The efficacy of a treatment combination of a COX‐2 inhibitor (meloxicam), chemotherapy and surgery in 23 cats with histologically confirmed mammary gland adenocarcinoma was evaluated. All of the cases underwent an aggressive surgery with concurrent doxorubicin‐based chemotherapy. Meloxicam was given orally starting the day after surgery and was continued indefinitely. Serum renal parameters were measured every 3–5 months. Three cats developed azotemia, whereas in four other renal parameters increased but remained within normal limit. The Kaplan–Meier median survival time was 460 days. The Kaplan–Meier median disease free interval was 269 days. The survival times are similar to other studies, not supporting the use of this treatment combination. Prospective studies with a higher number of cases are warranted to investigate the utility of this multimodality protocol for the treatment of feline mammary tumours.