IMAGING OF PHEOCHROMOCYTOMA IN 2 DOGS USING p-[18F] FLUOROBENZYLGUANIDINE

p-[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been developed as a positron emission tomography (PET) imaging radiopharmaceutical. Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The extent of the pheochromocytoma was well documented in both dogs on the PET study. The standardized uptake values within the pheochromocytomas were greater than 25 by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG study was normal. Surgical exploration and adrenal biopsy confirmed the [15F]PFBG imaging findings in both dogs. In each dog, there was rapid blood-pool clearance (within 10 min after intravenous administration of the [18F]PFBG), with high uptake specific within the myocardium and adrenal medulla. The results indicate that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in differentiating adrenal masses.     

EVALUATION OF 99MTC-DIETHYLENETRIAMINEPENTAACETIC ACID RENAL SCINTIGRAM CURVES IN NORMAL DOGS AFTER INDUCTION OF DIURESIS

The normal 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigram curve has 3 distinct phases; an arterial phase followed by progressive uptake and subsequent excretion from the kidney. In dogs with X-linked hereditary nephritis, a distinct flattening of the renal scintigram curve has been observed prior to any decline in glomerular filtration rate (GFR). The cause of this shape change is not known, however, it coincided with decreased urine-specific gravity and thus might be related to polyuria. To further evaluate this possibility, we assessed whether diuresis without concurrent renal disease could flatten the 99mTc-DTPA renal scintigram curve. GFR scintigraphy was performed in six healthy dogs once as a baseline, and again after induction of diuresis by each of four different methods. Scintigram curves were evaluated subjectively as well as quantitatively by calculation of GFR estimates, mean renal transit times, time to peak activity and half-time clearance. Complete flattening of the renal scintigram curve did not occur with diuresis alone, and therefore, flattening of the scintigram curve may serve as an early indicator of renal dysfunction. However, during diuresis after intravenous saline administration, alterations in time to peak activity and mean renal transit time may create inaccuracies in GFR estimates based on the conventional regression formula that cause a false lowering of the resultant global GFR value.     

COMPARATIVE STUDY OF INDIUM-111 LEUKOCYTES AND NEPHROSONOGRAPHY FOR DETECTION OF EXPERIMENTAL PYELONEPHRITIS IN DOGS

Nephrosonography was compared to In-111 WBC for detection of experimentally induced pyelonephritis in 12 dogs. Nephrosonography was performed during the acute and chronic phase of pyelonephritis in all dogs. Sonographic abnormalities were found in all infected kidneys imaged early after infection. In the chronic phase of pyelonephritis, the sonographic abnormalities had decreased in severity in 9 kidneys, increased in severity in 2 kidneys, and had resolved in 2 kidneys. After histopathologic evaluation, eleven of fifteen kidneys (73%) with pyelonephritis had been identified by sonography. The In-111 WBC scan was performed during the acute phase of pyelonephritis in 9 dogs and during the chronic phase in all dogs. During the acute phase of pyelonephritis, the WBC scan was positive in 8 of the 9 dogs (89%) on images acquired 24 and 48 hr after injection of the labelled WBC. During the chronic phase of pyelonephritis, the WBC scan was negative in all 12 dogs. The sensitivity of the In-111 WBC scan was poor compared to nephrosonography for detection of chronic pyelonephritis. In this study, optimal detection of renal infection/pyelonephritis by In-111 WBC may be dependent on the presence of clinical signs and leukocytosis in dogs. Even when leukocytosis is present, the In-111 WBC may fail to accumulate in the kidney in dogs with pyelonephritis, particularly if no clinical signs (fever, depression, inappetence) are present.     

IN VITRO EVALUATION OF CANINE GRANULOCYTES LABELED WITH 99mTC-HEXAMETHYLPROPYLENEAMINE OXIME:

Technetium-99m hexamethylpropyleneamine oxine (^99mTc-HMPAO) and Indium-111 oxine (¹¹¹In-oxine) labeled canine gramulocytes were evaluated in vitro over a six hour period. Labeling efficiency for ^99mTC-HMPAO and ¹¹¹In-oxine labeled granulocytes was 39.6%± 8.0% and 60.6%± 17.6% (mean ± SD) respectively. The mean in vitro elution of the radiolabel ranged from 8.7-14.0% for the ^99mTc-HMPAO grannulocytes and from 6.1-9.0% for the ¹¹¹In-oxine granulocytes. Mean cell viability, for the ^99mTc-HMPAO, ¹¹¹In-oxine and non-radiolabeled control granulocytes ranged from 97.8-99.4%, 96.4-98.5% and 98.2-99.0%, respectively. The phagocytic ability of the ^99mTc-HMPAO, ¹¹¹In-oxine and control granulocytes ranged from 47.5-54.1%, 38.9-56.2% and 46.6-57.8% respectively over the six hour study period. Although labeling efficiency using ¹¹¹In-oxine was significantly (P=0.05) better than ^99mTc-HMPAO, there was no significant difference in label retention of the two radiolabels. There was no significant difference in viability or phagocytic function during the six hour study period. Considering the potential cost advantage and the superior imaging qualities of Technetium-99m relative to Indium-111, ^99mTc-HMPAO appears to be a good alternative to ¹¹¹In-oxine as a granulocyte label.     

DIAGNOSIS OF ARTERIOPORTAL FISTULAE IN FOUR DOGS USING COMPUTED TOMOGRAPHIC ANGIOGRAPHY

Arterioportal fistulae are rare congenital anomalies of the hepatic vasculature. Diagnosis is conventionally made by selective angiography or ultrasonography. This report describes use of a dual-phase computed tomographic (CT) angiographic technique to diagnose arterioportal fistulae in four dogs. Advantages of this method include a noninvasive peripheral injection of contrast medium, ability to diagnose multiple acquired extrahepatic shunts, and observation of hemodynamic changes such as hepatofugal blood flow and reduced circulation to the caudal abdomen. The hepatic vasculature including arteries, veins, and portal veins can be completely evaluated. Dual-phase CT angiography is a safe and minimally invasive method of diagnosing arterioportal fistulae in dogs.     

EVALUATION OF LYMPHOMA IN A CAT USING 99mTc-SESTAMIBI

This report describes the evaluation of cutaneous lymphoma in a cat using 99mTc-sestamibi. A mass in the left pes with extension to the left popliteal lymph node was diagnosed as B-cell lymphoma. Thoracic and abdominal radiography and abdominal ultrasound were unremarkable. Scintigraphy using 99mTc-sestamibi confirmed the lesion was confined to the left hind leg, and the leg was amputated. The cat made a full recovery.     

QUANTITATIVE SURVEY RADIOGRAPHIC EVALUATION OF THE LUMBOSACRAL SPINE OF NORMAL DOGS AND DOGS WITH DEGENERATIVE LUMBOSACRAL STENOSIS

Survey radiographic studies of the lumbosacral region for 93 normal dogs and for 26 dogs with confirmed degenerative lumbosacral stenosis were reviewed. Normal dogs were divided into 9 groups based on age and body weight. For normal dogs, increasing age and body weight were associated with a decreased ability to extend the lumbosacral joint and with increased incidence and severity of spondylosis. Transitional lumbosacral vertebrae and evidence of lumbosacral disc space collapse were very infrequent findings, and the pivot point for lumbosacral motion was consistently centered over the lumbosacral disc space. Relative to an age/weight matched sub-population of normal dogs, dogs with degenerative lumbosacral stenosis had similar mean normalized lumbosacral vertebral canal height, larger mean neutral lumbosacral angle, decreased extension of the lumbosacral joint, increased flexion of the lumbosacral joint, reduced lumbosacral range of motion, increased lumbosacral dynamic malalignment, higher incidence and severity of spondylosis, higher incidence of transitional vertebrae, and higher incidence of lumbosacral disc space collapse. A logistic model based strictly on radiographic parameters was able to discriminate normal from affected dogs with an overall accuracy rate of 86%.     

SCINTIGRAPHIC GASTROINTESTINAL BLEEDING LOCALIZATION WITH 99mTc-LABELED RED BLOOD CELLS

Ten scintigraphic gastrointestinal bleeding localization examinations were done in nine dogs. All dogs had clinical evidence of gastrointestinal bleeding prior to or on the day of the examination. Scintigraphy was done by in vivo labeling of red blood cells with ^99mTechnetium and imaging serially with a gamma camera over a 21-hour period. Of the nine dogs, four case history reports are presented. Three of these dogs had positive scintigraphic examinations. One dog had a negative scan but was later shown to have been ingesting material that mimicked the appearance of melena.     

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.     

THORACIC AND ABDOMINAL ORGAN UPTAKE OF 2-DEOXY-2-[18F]FLUORO-d-GLUCOSE (18FDG) WITH POSITRON EMISSION TOMOGRAPHY IN THE NORMAL DOG

Positron emission tomography (PET) has found widespread application for staging and monitoring neoplastic diseases in humans. PET is becoming more available in veterinary medicine, therefore biodistribution of 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) in normal dogs is needed for lesion interpretation in disease states. A large field-of-view (FOV) PET scanner with a 70 cm bore diameter and a 53-cm FOV was used in this study to acquire dynamic ¹⁸FDG uptake data from parenchymal organs in seven normal dogs. A 2-h, dynamic list-mode acquisition was initiated simultaneously with intravenous ¹⁸FDG injection. Regions of interest (ROIs) were manually drawn over liver, spleen, left and right renal cortices, left ventricular free wall, and thymus. Standardized uptake values (SUVs) of these organs were calculated for 24 5-min frames over the 2-h acquisition. This SUV data from parenchymal organs of normal dogs compares favorably with those of normal humans and will be used in ongoing canine studies using PET to evaluate various diseases.     

COMPARISON BETWEEN THE SCINTIGRAPHIC UPTAKE AND PLASMA CLEARANCE OF 99mTc-DIETHYLENETRIAMINEPENTACETIC ACID (DTPA) FOR THE EVALUATION OF THE GLOMERULAR FILTRATION RATE IN DOGS

The scintigraphically measured percentage dose uptake of ^99mTc-DTPA by the kidneys and the plasma clearance of ^99mTc-DTPA have been reported to correlate well with inulin clearance. These two parameters were evaluated in seven dogs with known or suspected naturally occurring renal disease and compared to simultaneously measured renal inulin clearance. Correlation between inulin clearance and the ^99mTc-DTPA plasma clearance was better ( p =.0016) than the correlation between the percentage DTPA uptake by the kidney. It was concluded that measurement of ^99mTc-DTPA plasma clearance is a more accurate method to estimate global glomerular filtration rate (GFR) than the percentage kidney uptake.     

TRANSSPLENIC PORTAL SCINTIGRAPHY USING 99MTC-MEBROFENIN IN NORMAL DOGS

Transsplenic portal scintigraphy using sodium pertechnetate is superior to per-rectal portal scintigraphy due to improved visualization of the portal vasculature with decreased patient and personnel exposure. The purpose of this study was to describe the use of 99mTc-mebrofenin, the radiopharmaceutical of choice for the evaluation of hepatic function, in place of pertechnetate for transsplenic portal scintigraphy in normal dogs. Sixteen juvenile dogs underwent transsplenic portal scintigraphy using 37-130 MBq 99mTc-mebrofenin in a 0.2-0.5 ml volume. After the initial dynamic acquisition obtained at 4 frames/s in right lateral recumbency, static right lateral, and ventral views were obtained at 5, 10, 15, 20, 25, 30, 40, 50, and 60 min. A nuclear angiogram of the splenic and portal veins was visible in all dogs, followed by rapid distribution of the radiopharmaceutical in the liver. Hepatic morphology was more easily defined than with pertechnetate. Transit time could not be calculated due to the high hepatic extraction of 99mTc-mebrofenin. Mean +/- SD shunt fraction was 0.8 +/- 0.8%. Time to peak liver activity was 3.1 +/- 1.1 min, and hepatic excretion T1/2 was 19.4 +/- 6.3 min. No visible blood pool and cardiac activity was seen after 5 min. The mean +/- SD time to visualization of defined biliary activity was 8.8 +/- 2.9 min. Absorption from the spleen was significantly higher than that reported for pertechnetate (87.9 +/- 8.2%, vs. 52.5 +/- 19.1%). 99mTc-mebrofenin can be used in place of pertechnetate for transsplenic portal scintigraphy, with the advantage of combining quantitative parameters of liver function with the already known advantage of transsplenic portal scintigraphy.     

USE OF 123IODINE METAIODOBENZYLGUANIDINE SCINTIGRAPHY FOR THE DIAGNOSIS OF A PHEOCHROMOCYTOMA IN A DOG

A 13-year-old neutered female Yorkshire terrier presented with a history of progressive episodic weakness and disorientation of 4 months duration. Physical and neurologic examinations were normal at presentation. Abdominal ultrasound revealed a mass involving the right adrenal gland. Standard planar scintigraphy was performed at 4, 18, and 24 hours after intravenous injection 185 MBq (5mCi) of ¹²³I-labeled metaiodobenzylguanidine (¹²³I-MIBG). An area of focal intense uptake was identified in the area of the right adrenal gland. A pheochromocytoma was confirmed histologically after surgical excision.     

TREATMENT OF DIFFERENTIATED THYROID CARCINOMA IN 7 DOGS UTILIZING 131I

Seven dogs with thyroid gland carcinoma were treated with ¹³¹I and hormone suppressive therapy either alone (3 dogs) or in combination with surgery (3 dogs) or ¹³⁷Cs teletherapy and chemotherapy (1 dog). Empirically chosen doses of 75 to 137 mCi of ¹³¹I were given orally (2 dogs) and intravenously (5 dogs). Adverse effects were limited to acute, transient bone marrow hypoplasia and pancytopenia. Nominal objective reduction in tumor volume or size and number of pulmonary metastases was observed in 4 dogs treated with ¹³¹I and thyroxine. Of these 4 dogs, 2 had stable disease for periods of 4 and 12 months while a third dog had stable disease for 27 months following two ¹³¹I treatments at 3 month intervals. The fourth dog had progressive disease. Two dogs with mediastinal metastases showed reduction in localization of ^99mTc pertechnetate and radioiodine following 2 and 3 treatments using ¹³¹I. It appears that relatively high doses of ¹³¹I can be used safely for the treatment of canine thyroid tumors and that further investigation can be justified to define its efficacy.     

COMPARISON OF TRANSCOLONIC 123I-IODOAMPHETAMINE AND PORTAL VEIN INJECTION OF 99mTc-MACROAGGREGATED ALBUMIN SHUNT FRACTION CALCU-LATIONS IN EXPERIMENTAL DOGS WITH ACQUIRED POR-TOSYSTEMIC SHUNTS

Shunt fraction was determined using transcolonic ¹²³I-iodoamphetamine (IMP) and portal vein injection of ^99mTc-macroaggregated albumin (MAA) in a group of eight dogs with chronic cirrhosis and acquired portosystemic shunts subsequent to total common bile duct ligation. Hepatic parenchymal damage was confirmed by alterations in liver function tests and liver histology. Seven of the eight dogs developed portal hypertension and had angiographic evidence of hepatofugal portal blood flow with multiple peripheral portosystemic anastomoses. Shunt fractions determined in the seven dogs with shunts varied from 39 to 100 using IMP and 45 to 93 using MAA. The remaining dog had normal portal pressure, a normal portal angiogram, and normal IMP and MAA scintigraphic studies. There was an excellent correlation between the two methods of shunt fraction calculation (R²= 0.98) and the line of regression was not significantly different from unity (IMP = 1.09 × MAA - 0.03).     

EVALUATION OF HEART TIME-ACTIVITY CURVES AS A PREDICTOR OF HEPATIC EXTRACTION OF 99mTc-MEBROFENIN IN DOGS

In this study, heart time-activity curve, created following intravenous injection of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and dogs with induced hepatic parenchymal cell damage. The results were compared to a direct measurement of hepatic extraction following mesenteric venous injection of 99mTc-mebrofenin. The heart time-activity curves were normalized and the area under the curve from 0-30 minutes and 0-60 minutes were determined. In addition, the half-time clearance rate of the heart time-activity curve was analyzed using a two-compartment model. Linear regression analysis was used to describe the relationship between the area under the normalized heart time-activity curve and hepatic extraction. There was good correlation between the area under the normalized heart time-activity curve and hepatic extraction. The best correlation was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating hepatic extraction was derived using linear regression analysis: Hepatic extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation between the half-time clearance rates from the heart time-activity curve and hepatic extraction. The best correlation was between the fast phase half-time clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart time-activity curve can be used as a simple alternative to deconvolutional analysis for the determination of hepatic extraction as a measure of hepatic parenchymal cell function in the dog.     

18FDG-PET IMAGING IN CANINE LYMPHOMA AND CUTANEOUS MAST CELL TUMOR

Positron Emission Tomography (PET) using the glucose analog 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) is a common imaging modality for diagnosis and management of many human malignancies. We evaluated ¹⁸FDG-PET in dogs with either multicentric lymphoma (LSA) or cutaneous mast cell tumor (MCT). A prototype large field-of-view PET scanner was used to collect whole-body images in nine dogs with LSA or MCT. Both tumors were characterized by avidity for ¹⁸FDG. In dogs with LSA, ¹⁸FDG-PET correctly identified involvement of superficial and internal lymph nodes, liver, and spleen. Repeated PET scans after induction chemotherapy demonstrated resolution of abnormal ¹⁸FDG uptake within these sites. In dogs with MCT, ¹⁸FDG-PET correctly identified MCT metastasis to regional lymph nodes in all dogs in which this was suspected or confirmed with cytology or biopsy before the PET scan. In two dogs, additional sites of mast cell disease were identified with ¹⁸FDG-PET that were undetected on physical examination and/or regional lymph node cytology. ¹⁸FDG-PET holds promise as a whole-body staging method for canine LSA and MCT.     

USE OF TRANSCOLONIC 123I-IODOAMPHETAMINE TO DIAGNOSE SPONTANEOUS PORTOSYSTEMIC SHUNTS IN 18 DOGS

Transcolonic ¹²³I-Iodoamphetamine is rapidly absorbed across the colonic mucosa and binds to amine receptors in the liver and lungs. During the first ten minutes following colonic administration, a simple ratio of lung counts to lung counts plus liver counts provides an accurate estimate of the fraction of portal blood that bypasses hepatic sinusoids in dogs with portosystemic shunts. Studies were performed on 24 dogs with suspect portosystemic shunt. Shunt fraction values for 18 dogs with surgically confirmed portosystemic shunt were obviously higher than published values for normal dogs, and also significantly higher than values for the other six dogs, later confirmed to lack shunts. Postoperative studies were repeated on ten dogs with single shunt vessels 1–2 days after shunt closure. Total shunt ligation resulted in normal postoperative shunt fraction, whereas partial shunt ligation resulted in persistant elevation of shunt fraction. Transcolonic iodoamphetamine scintigraphy is noninvasive, easy to perform, and provides an accurate method to diagnose dogs with portosystemic shunt.     

EVALUATION OF THE URETER AND URETEROVESICULAR JUNCTION USING HELICAL COMPUTED TOMOGRAPHIC EXCRETORY UROGRAPHY IN HEALTHY DOGS

Abdominal computed tomography (CT) using a protocol designed for evaluation of the ureters was performed on six normal purpose-bred research dogs. After noncontrast CT, a postcontrast scan was performed 3 min post midpoint of injection of 400 mgI/kg body weight of diatrizoate meglumine/sodium. Ureteral and ureterovesicular junction anatomy were readily assessed with minimal patient preparation. The ureters were similar in size to reported values and the renal pelvis, ureter, and ureterovesicular junction were easily identified on both noncontrast and contrast-enhanced scans. There was a significant relationship between bladder volume and interureterovesicular junction distance but not between bladder volume and ureterovesicular junction to internal urethral orifice distance. A reliable bony landmark for the identification of the internal urethral orifice could not be determined. The results of this preliminary study of normal anatomy should facilitate the clinical use of CT in the evaluation of ureteral disease (e.g., ureteral ectopia).     

USE OF [123I]-2-IODO-l-PHENYLALANINE AS A TUMOR IMAGING AGENT IN TWO DOGS WITH SYNOVIAL CELL SARCOMA

[123I]-iodo-L-phenylalanine was successfully evaluated for gamma camera imaging in vivo in tumor-bearing athymic mice and in humans with brain tumors. Here, we report the use of this tracer in two dogs with synovial cell sarcoma of the tarsus. [123I]-iodo-L-phenylalanine was quantitatively prepared as a kit formulation using the Cu(1+) +-assisted nucleophilic exchange. Rapid [123I]-2-iodo-L-phenylalanine tumor accumulation was observed with good tumor to background contrast and rapid clearance in these two dogs. This radiopharmaceutical is a promising alternative tumor tracer to overcome the known limitations of 18F-fluorodeoxyglucose and, when labelled with radioiodine-131, has the potential to be used for therapeutic purposes.