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.     

THE USE OF99mTc RADIOAEROSOL VENTILATION AND MACROAGGREGATED ALBUMIN PERFUSION IMAGING FOR THE DETECTION OF PULMONARY EMBOLI IN THE DOG

This study was undertaken to design protocol for use of radioaerosol of technetium-99m-labeled diethylenetriaminepentacetic acid (^99mTc-DTPA) for ventilation imaging as clinical tool in the dog and to evaluate imaging characteristics in both normal dogs and dogs with simulated pulmonary embolism. Clearance of the 99mTc-DTPA radioaerosol from the lung was also evaluated. Six normal dogs were used in two phases: (1) as their own controls and (2) during pulmonary artery occlusion using Swan-Ganz catheter. Radioaerosol ventilation images were obtained and rate of clearance from normal and occluded lungs determined. Perfusion studies using technetium-99m-macroaggregated albumin (^99mTc-MAA) immediately followed. Clearance half-times (T_1/2) were found to be significantly increased (p < 0.05) in acutely occluded lungs; however, the small magnitude of this change was visually difficult to detect on the ventilation images. Good quality initial ventilation and perfusion images were obtained and provided ready evaluation of ventilation (V), perfusion (Q), and induced V/Q mismatches. A clinical case of pulmonary thromboembolic disease was also evaluated with diagnostic result, indicating that this method of V/Q scintigraphy can provide useful information in those clinical cases in which pulmonary thromboembolism is suspected.     

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.     

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.     

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.     

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.     

Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1Δ mutation) and extrinsic (ketoconazole treated) P-glycoprotein deficiency

P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to play a role in the biliary excretion of a variety of drugs, but specific studies in dogs have not been performed. Because a number of endogenous (ABCB1 polymorphisms) and exogenous (pharmacological P-gp inhibition) factors can interfere with normal P-gp function, a better understanding of P-gp's role in biliary drug excretion is crucial in preventing adverse drug reactions and drug–drug interactions in dogs. The objectives of this study were to compare biliary excretion of technetium-99m-sestamibi (^99mTc-MIBI), a radio-labelled P-gp substrate, in wild-type dogs (ABCB1 wild/wild), and dogs with intrinsic and extrinsic deficiencies in P-gp function. Dogs with intrinsic P-gp deficiency included ABCB1 mut/mut dogs, and dogs with presumed intermediate P-gp phenotype (ABCB1 mut/wild). Dogs with extrinsic P-gp deficiency were considered to be ABCB1 wild/wild dogs treated with the P-gp inhibitor ketoconazole (5 mg/kg PO q12h × 9 doses). Results from this study indicate that ABCB1 mut/mut dogs have significantly decreased biliary excretion of ^99mTc-MIBI compared with ABCB1 wild/wild dogs. Treatment with ketoconazole significantly decreased biliary excretion of ^99mTc-MIBI in ABCB1 wild/wild dogs. P-gp appears to play an important role in the biliary excretion of ^99mTc-MIBI in dogs. It is likely that concurrent administration of a P-gp inhibitor such as ketoconazole will decrease P-gp-mediated biliary excretion of other substrate drugs as well.     

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.     

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.     

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.     

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.     

99mTc-METHOXY-ISOBUTYL-ISONITRILE (SESTAMIBI) IMAGING OF MALIGNANT CANINE LYMPHOMA

Technetium-99m methoxy-isobutyl-isonitrile (sestamibi) imaging of malignant canine lymphoma was performed in thirteen dogs 1 hour after intravenous injection of ^99mTc-sestamibi at 13 MBq (0.35 mCi) per kilogram body weight. Abnormal tracer uptake was visualized in the liver, spleen, bone marrow, and mesenteric, inguinal, popliteal, sternal, cranial cervical and mandibular lymph nodes. Radiopharmaceutical uptake was also noted in a nasal mass. One large neoplastic renal mass did not have demonstrable sestamibi uptake. Other regions had no significant difference in the target:background ratios when compared with values from normal dogs ( P > 0.05). ^99mTc-sestamibi can be used to image malignant lymphoma, and has potential applications in the management of patients to document response to treatment and to stage of extent of disease.     

Effect of meloxicam and carprofen on renal function when administered to healthy dogs prior to anesthesia and painful stimulation

OBJECTIVE: To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine. ANIMALS: 6 male and 6 female healthy young-adult Beagles. PROCEDURE: A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia. RESULTS: Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.     

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.     

SCINTIGRAPHIC ASSESSMENT OF DISTAL EXTREMITY PERFUSION IN 17 PATIENTS

To assess the role of scintigraphic evaluation of distal limb perfusion, the medical records and scintigraphic perfusion images of 17 animals(8dogs, 2cats, 2calves, 4birds and 1 ferret) with clinical signs of distal limb ischemia were examined retrospectively. Images were obtained at 5 and 10 minutes following injection of ^99m Tc-MDP, or ^99mTc-DTPA. The initial scintigraphic diagnoses of 17 animals included complete ischemia(8/17), partially reduced perfusion(5/17), and normal to increased perfusion(4/17). In 4 of the animals with partially reduced perfusion, follow-up scans indicatd progression to complete ischemia(1/4) or normal to increased perfusion(3/4). Nine of 17 animals had a final scintigraphic diagnosis of complete distal limb ischemia, and these animals were either euthanized(5/9)or had limb amputation(4/9).A final diagnosis of complete ischemia was supported with either repeat scanning(3/10), continued clinical observation(6/10)and /or pathological examination(10/10).Clinical Scintigraphy provided a safe and noninvasive assessment of distal limb perfusison, which corresponded with clinical outcome.     

CANINE VENTRAL BODY WALL LYMPHOSCINTIGRAPHY

The scintigraphic characteristics of lymph nodes draining the ventral body wall were analyzed in 12 dogs as to their pattern of appearance and image contrast. Each dog was scanned using ^99mTc-antimony sulfide colloid and ^99mTc-dextran, and the imaging characteristics of these agents were compared. A large degree of variability exists in the number and pattern of lymph node appearance with either agent. No significant difference in average numbers of lymph nodes per dog was shown between agents. However, ^99mTc-antimony sulfide colloid provided a significantly (p<.05) better target-to-background ratio, which determines the contrast with which lymph nodes stand out from background activity. From these findings, it is suggested that too great a variability in lymph node appearance exists using this procedure to allow a high degree of confidence in the diagnosis of metastasis to lymph nodes of the ventral body wall. However, for other purposes, ^99mTc-antimony sulfide colloid is the lymphoscintigraphic agent of choice.     

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.     

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.     

Effect of tepoxalin on renal function in healthy dogs receiving an angiotensin-converting enzyme inhibitor

The objective of this study was to investigate renal function in clinically normal dogs receiving tepoxalin, a nonsteroidal inflammatory drug, either in association with or without an angiotensin-converting enzyme inhibitor (ACEI). Ten adult female Beagle dogs were used in the three phases of the study. The dogs were administered the drugs once daily for 7 days (experiment 1: placebo/tepoxalin/tepoxalin and benazepril; experiment 2: enalapril/tepoxalin and enalapril) or for 28 days (experiment 3: tepoxalin and benazepril together). Renal function was assessed by measurement of glomerular filtration rate (GFR) by renal scintigraphy [(renal uptake of 99mTc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of 99mTc-DTPA. Compared with the placebo group, renal uptake and plasma clearance of 99mTc-DTPA were not significantly modified after a 7-day period of treatment with tepoxalin or enalapril alone, tepoxalin and benazepril or tepoxalin and enalapril together. No significant change was obtained in GFR after a 28-day period of dosing with tepoxalin and benazepril together. Therefore, it was concluded that tepoxalin did not alter renal function in healthy Beagle dogs receiving ACEI.