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.     

Frequency of pulmonary mineralization and hypoxemia in 21 dogs with pituitary-dependent hyperadrenocorticism

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using ^99mTc-methylene diphosphonate (^99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were pro-spectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using ^99mTc-macro-aggregated albumin [^99mTc-MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco-lumbar vertebrae from lateral thoracic ^99mTc-MDP images. Thoracic: vertebral ratios were calculated using ^99mTc-MDP studies from 21 control dogs. The thoracic: vertebral ratios were compared between the 2 groups (PDH and control). The mean age (±SD) of the 21 PDH dogs was 10.2 (±3) years, whereas the mean age of the control group was 9.8 (±3) years. Seven of the 21 dogs with PDH were hypoxemic (denned as an arterial partial pressure of oxygen [PaO₂] <80 mm Hg) with an average PaO₂ (±SD) of 62 (±15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using ^99mTc-MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic: vertebral ratio was not significantly different between the PDH and control dogs (0.5 ± 0.4 versus 0.4 ± 0.1, P = .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.     

QUANTITATIVE THYROID SCINTIGRAPHY IN GREYHOUNDS SUSPECTED OF PRIMARY HYPOTHYROIDISM

The existence of hypothyroidism in greyhounds remains controversial and its investigation is complicated by the low circulating thyroid hormone concentrations typically found in healthy dogs of this breed. Quantitative measurement of thyroidal technetium-99m pertechnetate (^99mTcO₄⁻) uptake is known to be useful in assessing thyroid function in other breeds. The aim of this study was to evaluate thyroid scintigraphy as a method of assessing thyroid function in greyhounds suspected of primary hypothyroidism. Twenty greyhounds (eight females, 12 males) were studied. Thirteen had bald thigh syndrome and seven poor performance and low total T4. Total T4 concentrations were decreased in 18 (90%), and free T4 in two (10%) dogs. All canine thyroid stimulating hormone concentrations were within the reference interval. Thyroidal ^99mTcO₄⁻ uptake values (mean ± SD, 0.76 ± 0.26%) were within the reference limits published for euthyroid dogs (0.39–1.86%) making hypothyroidism highly unlikely. There were no significant differences ( P <0.05) when comparing data between dogs with bald thigh syndrome (13 dogs) and the remaining dogs (seven dogs). Seventeen (85%) dogs had higher uptake in the left thyroid gland than in the right that might reflect an anatomic feature of the greyhound breed. Calculation of percent thyroidal uptake of ^99mTcO₄⁻ is more accurate than thyroid:salivary gland ratios because of high variability in salivary gland uptake. Percent thyroidal uptake of ^99mTcO₄⁻ should be used when assessing thyroid function scintigraphically in the greyhound breed.     

THE INSENSITIVITY OF 99mTc PERTECHNETATE FOR DETECTING METASTASES OF A FUNCTIONAL THYROID CARCINOMA IN A DOG

This report describes the use of ^99mtechnetium pertechnetate (^99mTcO₄⁻) and ¹³¹[for imaging of a metastatic thyroid carcinoma in a dog. The ¹³¹] imaging showed metastatic lesions undetected by the ^99mTcO₄⁻ imaging on 2 separate occasions. The possible mechanisms for the discrepancies between ¹³¹I and ^99mTcO₄⁻ imaging of thyroid carcinomas are discussed. The use of ¹³¹I for the imaging of functional thyroid carcinomas in the dog is recommended.     

QUALITATIVE AND QUANTITATIVE THYROID IMAGING IN FELINE HYPERTHYROIDISM USING TECHNETIUM-99M AS PERTECHNETATE

Thyroid imaging using technetium-99m as pertechnetate (^99mTcO₄) was carried out in five healthy, euthyroid and 37 hyperthyroid cats using both pinhole and parallel-hole collimators. Images of greater resolution, necessary to distinguish bilateral lobe involvement, were obtained using the pinhole collimator. Per cent thyriod ^99mTcO₄ - uptake was calculated in each cat and was significanly (P < 0.001) higher in hyperthyroid compared with euthyroid cats. In the hyperthyroid cats, per cent thyroid uptake was significantly correlated with serum total thyroxine (T4) and triiodothyronine (T3) Concentrations. Per cent thyroid ^99mTcO₄ - uptake is increased in feline hyperthyrodism and may be calculated using a pinhole collimator alone at the time of qalitative assessment of the extent of thyroid tissue involvement.     

IN-VIVO TESTING OF TECHNETIUM-99m-LABELED MONOCLONAL ANTIBODIES SPECIFIC FOR DIROFILARIA IMMITIS

Monoclonal antibodies specific for Dirofilaria immitis were labeled with technetium-99m (^99mTc) and tested in vivo in five heartworm positive and five heartworm negative dogs. Diethlyenetriaminepentaactic acid (DTPA) was used to label the ^99mTc to the antibody. Radiochemical purity of the ^99mTc-labeled antibodies (^99mTc-MoAb) was determined by gel filtration and by instant thin-layer chromatography. The uptake percentages in the blood, heart, lung, liver, and kidneys were determined from tissues obtained at necropsy and by computer analysis of images obtained at two and 24 hours. The percent uptake in the heart region of interest (ROI) at two hours was significantly higher in the heartworm-positive dogs. There was significant correlation between the uptake in the heart at two hours to the number and activity of the worms at necropsy.     

LYMPH NODE UPTAKE OF 99MTc-MDP DURING BONE SCINTIGRAPHY IN DOGS

Localization of ^99mTc-MDP in lymph nodes was apparent on the three-hour bone-scan image in seven dogs. In six dogs injection or leakage of the radiopharmaceutical into the perivascular tissues was associated with subsequent uptake in an ipsilateral lymph node. In the remaining dog, ^99mTc-MDP localized in a lymph node infiltrated by metastatic osteosarcoma. This aided staging of the tumor. Possible mechanisms of ^99mTc-MDP localization in soft tissues are briefly reviewed.     

DETECTION OF PORTAL BLOOD FLOW USING PER-RECTAL 99mTc-PERTECHNETATE SCINTIGRAPHY IN NORMAL CATS

This study reports data obtained from per-rectal ^99mTc-pertechnetate portal scintigraphy in normal cats. It examines the effects of chemical restraint and the methods employed in defining regions of interest (ROIs) on the shunt index derived from this data. Six normal cats were used for the study; all six were chemically restrained for imaging using propofol and later four of them were manually restrained for comparison. Portal blood flow was studied and the mean shunt index was found to be 5.9%± 3.9 when ROIs were operator defined and 9.2%± 4.4 when ROIs were defined using an isocontour program. In cats that were restrained using propofol and operator defined ROIs, the mean value for the time between detection of radioactivity in the liver and in the heart was 14 ± 1 seconds.     

PULMONARY MINERALIZATION IN FOUR DOGS WITH CUSHING'S SYNDROME

The clinical and imaging features of four dogs with Cushing's syndrome and pulmonary mineralization are reviewed. Three dogs presented with a primary complaint of respiratory distress/dyspnea. Three dogs had pituitary dependent Cushing's syndrome, while the remaining one dog had iatrogenic Cushing's syndrome. Each dog had clinical features typical for Cushing's syndrome. Two of the dogs were euthanized due to progressive hypoxemia. In each dog, the serum calcium, phosphorous, blood urea nitrogen and creatinine were normal.
A generalized increase in unstructured interstitial pulmonary opacity with diffuse mineralization was noted on thoracic radiographs of all dogs. In one dog, an ill-defined nodular interstitial pattern of mineralization was present. Delayed bone phase scintigraphy using ^99mTechnetium methylene diphosphonate documented generalized pulmonary uptake in two dogs. ^99mTechnetium labeled microaggregated albumin lung perfusion scans were normal in these two dogs. ^99mTc-MDP scintigraphy can provide useful information in diagnosing pulmonary mineralization in Cushingoid dogs.     

QUANTITATIVE HEPATOBILIARY SCINTIGRAPHY USING 99mTC-DISIDA IN THE DOG

Quantitative hepatobiliary scintigraphy using ^99mTc-2,6 diisopropylphenylcarbamoylmethyl iminodiacetic acid (DISIDA) was performed in normal dogs. ^99mTc-DISIDA is excreted by the hepatocyte into the biliary tract. Hepatic blood flow from arterial and portal venous sources was measured as the hepatic perfusion index. The hepatic clearance of the radiopharmaceutical was used to assess hepatocyte function and parenchymal biliary transport. Biliary ejection was evaluated using synthetic cholecystokinin infusion. The procedure should be useful in evaluating dogs with hepatic and biliary disease.     

VALIDATION OF DECONVOLUTIONAL ANALYSIS FOR THE MEASUREMENT OF HEPATIC FUNCTION IN DOGS WITH TOXIC-INDUCED LIVER DISEASE

The extraction of the hepatobiliary radiopharmaceutical ^99mTc-mebrofenin ( Choletec ) by the liver can be used to evaluate the severity of hepatocellular disease. The hepatic parenchymal cells extract mebrofenin from the blood by the same active transport mechanism as bilirubin. The ability of the liver to extract ^99mTc-membrofenin is a measure of hepatic parenchymal cell function. In this study, we induced hepatocellular disease by administration of a hepatotoxic drug and compared a direct method of determining the hepatic extraction of ^99mTc-membrofenin to hepatic extraction fraction derived from deconvolutional analysis. We also compared both methods of calculating the hepatic extraction of ^99mTc-membrofenin to liver histopathology. Hepatic extraction fraction derived from deconvolutional analysis correlated very well to the direct measurement technique (R=0.922, p<0.001). Both methods of determining hepatic extraction correlated well to quantitative histopathology, having the same correlation coefficient and p values. (R=-0.833, p=0.003). As the hepatic extraction ^99mTc-membrofenin decreased, the severity of the histopathologic lesions of the liver increased in a linear fashion. There was a significant correlation of the hepatic excretion T_1/2 to quantititative histopathology (R=0.949, p<0.001). The hepatic excretion T_1/2 increased as the severity of the histopathologic lesions of the liver increased. Hepatic extraction (HEF) and excretion of ^99mTc-membrofenin are good predictors of the severity of hepatocellular damage in toxic induced liver disease. This study helps validate the premise that HEF derived from deconvolutional analysis ois a good predictor of the actual first pass hepatic extraction of ^99mTc-membrofenin.     

IMAGING DIAGNOSIS—DUODENAL DIVERTICULUM IN A DOG

A young female Boxer had a history of chronic soft stool. Survey abdominal radiographs were unremarkable. A duodenal diverticulum was identified in abdominal ultrasound and barium upper-gastrointestinal contrast examinations. Before surgery a ^99mTc-pertechnetate study was performed to evaluate for ectopic gastric mucosa in the duodenal diverticulum. Focal abnormal increased radioactivity was identified in the right caudal abdominal quadrant. The diverticulum was excised. Upon histopathologic examination of the duodenal diverticulum, ectopic gastric mucosa was not identified but ectopic pancreatic tissue was found. Mild eosinophilic inflammation within the diverticulum was suspected to be the cause of the mild ^99mTc uptake seen in this dog.     

UPTAKE OF 99mTCMDP IN MUSCLE ASSOCIATED WITH A PERIPHERAL NERVE BLOCK

A focal area of increased uptake of radioactivity was observed in muscle during bone imaging with ^99mTcMDP. The area was previously the site of a peripheral nerve block with mepivacaine hydrochloride. Additional experiments were done to document the action of the local anesthetic. The effect on uptake decreased over several days.     

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.     

TECHNETIUM-99M AND IODINE-131 THYROID SCINTIGRAPHY IN NORMAL AND RADIOTHYROIDECTOMIZED COCKATIELS (NYMPHICUS HOLLANDICUS)

Thyroid scintigraphy using sodium ^99mTechnetium pertechnetate (⁹⁹TcO₄-) was performed in normal and radiothyroidectomized cockatiels ( Nymphicus hollandicus ). ¹³¹I scintigraphy was performed in the course of ablating the thyroid glands. The thyroid glands in normal birds were clearly visualized, but were not individually resolvable. Thyroid glands were not visualized in thyroid-ablated birds. With ^99mTcO₄ scans, thyroid (or other region of interest)/body count density ratios were used for comparisons of normal and thyroid-ablated birds. Normal ^99mTcO₄- thyroid/body ratios (mean +/− SD) for the dorsal and lateral views were 1.83 +/− 0.31 and 1.70 +/− 0.34 respectively. Pertechnetate thyroid/body count density ratios decreased (to 0.93 -/−0.14 and 0.88 +/− 0.12 for dorsal and lateral views respectively) after thyroid ablation, while crop/body ratios increased. ^99mTcO₄- thyroid scintigraphy, therefore, was capable of detecting hypofunctional thyroid abnormalities in ¹³¹I radiothyroidectomized cockatiels.     

IN VITRO TESTING OF 99mTc-LABELED MONOCLONAL ANTIBODIES SPECIFIC FOR DIROFILARIA IMMITIS

Monoclonal antibodies specific for Dirofilaria immitis were labeled with technetium-99m (^99WTc), and their affinity was assessed in vitro. Of six monoclonal antibodies tested, three were IgG and three were IgM. A canine polyclonal IgG was used to establish the labeling technique and later as a control. Diethylenetriaminepentaacetic acid (DTPA) was used as a bifunctional chelator to bind ^99mTc covalently to the antibody. Radiochemical purity was measured with the use of gel filtration by a Sephadex G-25 column linked to an absorbance monitor and with instant thin-layer chromatography. The radiochemical purity had no significant influence on percent uptake on the heartworms. The clone designated as Di 130.1 had a significantly higher percent uptake than other clones tested.     

IMAGING DIAGNOSIS—ENOSTOSIS-LIKE LESION IN THE FEMUR OF A HORSE

An enostosis-like lesion was diagnosed in the left femur of a Swedish Warmblood horse that had a left hindlimb lameness of 3 weeks duration. With scintigraphy using technetium 99m-hydroxymethylene diphosphonate (^99m Tc-HDP) a marked regional focal increase in radioactivity was identified in the medullary cavity of the left femur. Radiographically there was a corresponding focal increase in bone opacity in the middiaphysis of the left femur. Histopathologically, a 5 cm area of bone matrix was present in the diaphysis of the left femur and confirmed as an enostosis-like lesion. Enostosis-like lesions should be considered as a source of pain in horses with difficult to localize, moderate to severe chronic lameness.     

SCINTIGRAPHIC MEASUREMENT OF UTERINE CLEARANCE IN MARES

Uterine clearance of technetium 99m-albumin colloid (^99mTc-μAA) was qualitatively and quantitatively measured in 5 reproductively normal mares and 5 mares susceptible to endometritis (infertile). The percentage of 370 MBq ^99mTc-μAA cleared from the uterine lumen within 2 hr of intrauterine infusion was measured in 10 mares on day 3 of estrus and 48 hr after ovulation. The procedure was repeated 3 times on day 3 of estrus in 6 mares to determine repeatability. Six mares were infused with 1110 MBq ^99mTc-μAA on day 3 of estrus to evaluate the effect of increasing the dose to reduce the imaging time. There was no statistically significant difference in the mean percentage of radiocolloid cleared from the uterus during day 3 of estrus or 48 hr after ovulation or in the percent cleared when the studies were repeated in individual mares. There was no statistically significant difference in uterine clearance between the 370 and 1110 MBq dose studies in each mare from 15 to 120 min. Reproductively normal mares cleared approximately 50% of the radiocolloid from the uterus by 120 min while susceptible mares cleared less than 15%.     

Nuclear Medical Bone Imaging and Targeted Radiography for Evaluation of Skeletal Neoplasms in 23 Dogs

Nuclear medical bone imaging was used in combination with targeted radiography to detect metastatic or multicentric lesions in 23 dogs with skeletal neoplasms. Each dog with a radio-graphically diagnosed skeletal neoplasm was injected with Technetium-99m labeled methylene diphosphonate (^99mTc-MDP) (15.0 mCi intravenously) for whole body imaging. All areas with increased uptake of ^99mTc-MDP were radiographed. In 19 dogs, the amount of bone shaft involvement in primary sites indicated by bone imaging was larger than the amount indicated by radiography. Eighteen dogs had secondary areas of increased ^99mTc-MDP uptake, six of which had secondary areas that were suspected radiographically to be neoplastic. Four dogs had lesions characterized histologically as neoplasia, one as bone infarction and one as normal cortical bone. Positive predictive value for this strategy was 66.7%. Results of this study suggest that nuclear medical bone imaging with targeted radiography is a quick, noninvasive technique with a good positive predictive value for evaluation of the skeleton for metastatic or multicentric sites of neoplasia.     

QUANTITATIVE99mTc-PERTECHNETATE THYROID SCINTIGRAPHY IN NORMAL BEAGLES

This study was done to investigate the validity of published canine thyroid/salivary (TS) rations of approximately i in normal dogs and to detemine thyroid uptak of ^99mTc-pertechnetate (pertechnetate) measured as percent uptake of injected dose. These parameters were evaluated in 13 Beagle dogs over a 4 hour period. Mean ± standard deviation (SD) and median T/S ratios of 1.2 ± 0.3 and 1.1 were essentially the same at twenty minutes and 1 hour. T/S Values ranged from 0.9 to 2.2 at 20minutes and from 0.8 to 2.4 at 1 hour. T/S ratio values progressively declined over the subsequent time intervals with mean ± SD and median values of 0.6 ± 0.2 and 0.6, respectively, measured at 4 hour. The mean with a rang of 0.28% to 0.90%. The mean ± SD time interval from injection of pertechanetate to maximum uptake within the thyroid gland was 160 ± 55 minutes with a range 31–240 minutes. The data derived from this study of normal dogs may be useful in the evaluation of dogs with thyroidal diseases including hypthyroidism