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.     

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.     

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.     

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.     

Radiographic and Scintigraphic Evidence of Focal Pulmonary Neoplasia in Three Cats With Hyperthyroidism: Diagnostic and Therapeutic Considerations

Three cats were diagnosed as hyperthyroid based on clinical signs, historical findings, laboratory abnormalities, and basal serum thyroxine (T₄) concentrations, and/or nuclear thyroid scans. Additionally, a presumptive diagnosis of thyroid carcinoma with pulmonary metastasis was made in each cat based on radiographic or scintigraphic evaluation. All three cats had solitary pulmonary nodules 1.5 to 2 cm in diameter on survey thoracic radiographs; one cat also had chylous pleural effusion and pulmonary lobar consolidation. Focal pulmonary accumulation of sodium pertechnetate (^99mTcO₄ -) and/or radioiodine (¹³¹I) corresponding to radiographic lesions were seen in all cats. Two cats were treated with single ablative doses (1111 to 1480 MBq) of¹³¹I; the remaining cat was euthanatized.
One of the treated cats died 8 days later; the other cat was euthanatized 22 weeks following treatment. Histopathologic examination of tissue obtained at necropsy confirmed metastatic thyroid carcinoma in one cat and bronchogenic adenocarcinoma in two cats. Our findings indicate that increased radionuclide uptake in focal pulmonary lesions and cytologic evaluation of tissue obtained by fine-needle aspiration are not specific for thyroid tissue. (Journal of Veterinary Internal Medicine 1993; 7:303–308. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

131‐I therapy for Advanced, Unresectable Thyroid Tumors in Dogs

Introduction:  Greater than 50% of dogs with thyroid tumors present with surgically unresectable disease for which external beam radiotherapy has been reported to prolong survival. The success of ¹³¹I for control of thyroid tumors in cats and in humans suggests such therapy may also play a role in the management of canine thyroid cancer.
Methods:  Thirty‐nine dogs with WHO stage II/III (invasive or ectopic; n = 32) or IV (metastatic; n = 7) thyroid tumors were treated with ¹³¹I alone. Changes in thyroid function, ^99MTc‐pertechnetate (^99MTc) scintigraphic changes, and tumor response were recorded. Dogs with ventral cervical tumors were evaluated for feasibility of surgical resection following ¹³¹I.
Results:  Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.
Conclusions:  These findings suggest ¹³¹I should be investigated more thoroughly in dogs with thyroid tumors not considered surgical candidates to more clearly characterize the indications for therapy and followup recommendations. ¹³¹I dosimetry in dogs with thyroid tumors remains problematic. Administration of ¹³¹I is currently based on empiric recommendations and, in general, the treatment is well tolerated although additional studies are indicated to optimize response and minimize toxicity.     

Quantitative Aspects of Thyroid Scintigraphy With Pertechnetate (99mTcO4) in Cats

Thyroidal ^99mTcO₄(pertechnetate) uptake percentages were determined in unanesthetized euthyroid (n = 13) and hyperthyroid (n = 18) cats. Maximal uptakes were observed 60 minutes after IV injection of the radionuclide and ranged from 0.3 to 3.9% of the dose in euthyroid cats (median 2.23%) and from 5.2% to 23.9% of the dose in hyperthyroid cats (median 14.8%) ( P < .05). There were no overlaps in pertechnetate uptake percentages during any of the intervals evaluated. It is concluded that the optimal time for visualization of the thyroid by ^99mTcO₄-scanning is 60 minutes after IV injection of the radionuclide. Calculation of the percentage uptake is of additional diagnostic value.     

COMPARISON OF PER-RECTAL PORTAL SCINTIGRAPHY USING 99mTECHNETIUM PERTECHNETATE TO MESENTERIC INJECTION OF RADIOACTIVE MICROSPHERES FOR QUANTIFICATION OF PORTOSYSTEMIC SHUNTS IN AN EXPERIMENTAL DOG MODEL

Per-rectal portal scintigraphy using tech-netium-99m pertechnetate (^99mTcO₄^-) was performed in 8 normal dogs before and after surgical creation of a portacaval shunt. Shunt fractions were calculated by computer assisted analysis of dynamic images (IMG) and compared to shunt fractions determined by mesenteric venous injection of radioactive microspheres (MIC). The mean pre-operative shunt fraction was 1.59% using IMG and 3.00% using MCI. The mean postoperative shunt fraction was 64.56% using IMG and 69.56% using MIC. There was excellent correlation between both methods (r² 0.94). Per-rectal portal scintigraphy is an easily performed, inexpensive method to diagnose and quantify portosystemic shunts in 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.     

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.     

Canine Thyroid Carcinomas: Clinical Occurrence, Staging by Means of Scintiscans, and Therapy of 15 Cases

Tumor characteristics and degree of metastatic disease are outlined for 15 cases of canine thyroid carcinoma based on physical, laboratory, and radiographic examinations. Results of thyroid scintiscans using sodium pertechnetate are discussed in relation to clinical staging. Surgical resection was the primary therapy. Adjuvant therapy included thyroid replacement therapy, and ¹³¹I and ⁶⁰Co radiotherapy.     

DIPHOSPHONATE TREATMENT OF A PRIMARY OSTEOSARCOMA IN A DOG: A CASE REPORT

The following sequence of treatments was administered to a Saint Bernard dog with a primary distal right radius osteosarcoma: 54 days of daily disodium 1-hydroxyethylidenediphosphonate (HEDP) subcutaneous injections; 53 days of HEDP per os ; one ³²P-HEDP intravenous injection. During the pretreatment period, there was an extensive increase in calcific tumor growth and osteoblastic proliferation. After the subcutaneous HEDP treatment, almost complete tumor necrosis was seen. After the oral HEDP treatment, only the deepest tumor portion contained active osteoblasts, calcific growth of the tumor was completely blocked, and uptake of ^99mTc-Sn-HEDP was reduced to one fourth of the pretreatment uptake. After a single ³²P-HEDP dose, large areas of tumor necrosis were evident histopathologically. However, subsequent resumption of cellular activity occurred in the tumor, and the uptake of ^99mTc-Sn-HEDP increased to pretreatment values. These data suggest that systemically administered HEDP should be studied further for its possible therapeutic potential in the treatment of osteosarcoma and indicate a need for further study of ³²P-HEDP or possibly ³³P-HEDP.     

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.     

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.     

IN VITRO EVALUATION OF FELINE LEUKOCYTES RADIOLABELED IN WHOLE BLOOD WITH 99MTC STANNOUS COLLOID

Technetium-99m stannous colloid (^99mTcSnC) has been used to radiolabel human leukocytes to investigate various inflammatory disorders. We investigated the in vitro behavior of feline leukocytes labeled in whole blood with ^99mTcSnC. Heparinized blood samples were collected from healthy cats and divided into control and test aliquots. The latter were labeled with ^99mTcSnC using a standard procedure. Leukocyte viability was determined for each sample using a trypan blue exclusion test. Labeling efficiency was determined for test aliquots. Test aliquots were layered onto Histopaque-1077^® and centrifuged before measurement of radioactivity of the blood components. Leukocytes from radiolabeled and control samples were washed and incubated with opsonized zymosan particles to allow assessment of phagocytic function. Aliquots were taken from radiolabeled feline leukocyte samples at 1, 3, 4, and 7 h postlabelling. After centrifugation of each aliquot, radioactivity of the supernatant and pellet was measured and the labeling retention determined. Leukocyte viability in both radiolabeled and control samples was >98%. The labeling efficiency was 95.2±0.14%. The distribution of radioactivity in feline blood was found to be 3.4±0.18% in plasma, 39.0±0.37% in erythrocytes, and 57.6±0.38% in leukocytes. Labeled feline leukocytes had phagocytic activity of 90.9±0.18% (control 91.3±0.15%). The radiolabeled leukocytes retained 93.4±0.19% of the radioactivity up to 7 h postlabeling. ^99mTcSnC efficiently labeled feline leukocytes with no effect on viability and minimal effect on phagocytic function. The percentage retention of radioactivity by the leukocytes was still high at 7 h postlabeling.     

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.     

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).     

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.     

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.     

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.