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.     

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.     

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.     

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.)     

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.     

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.     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

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     

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.     

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.     

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.     

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.     

THE NON-CARDIAC DISTRIBUTION OF 99mTC-METHOXY-ISOBUTYL-ISONITRILE (SESTAMIBI) IN NORMAL BEAGLES

Technetium-99m methoxy-isobutyl-isonitrile (sestamibi) is a radiophartnaceutical used for the evaluation of myocardial perfusion. Increased uptake of sestamibi has also been documented in tumors. The objective of this study was to document the extracardiac biodistribution of ^99mTc sestamibi in the normal dog. Nine normal beagles were given 0.35 mCi/kg ^99mTc sestamibi intravenously, and 60 second images were made of the entire body at 1 hour post injection. A defined distribution pattern was recognized, with good visualization of the heart, liver, gallbladder, small intestine, kidneys, urinary bladder, popliteal lymph nodes, parotid salivary glands and zygomatic salivary glands. Splenic uptake was not seen.
Target to background ratios were calculated for all the regions listed, using background regions-of-interest with the smallest coefficient of variance for the denominator. The mean, range and standard deviation of these ratios are given.     

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

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

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.     

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.     

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.     

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.     

EFFECTS OF METHIMAZOLE ON THYROID GLAND UPTAKE OF 99MTC-PERTECHNETATE IN 19 HYPERTHYROID CATS

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.     

EVALUATION OF RENAL HEMODYNAMICS IN AWAKE AND ISOFLURANE-ANESTHETIZED CATS WITH PULSED-WAVE DOPPLER AND QUANTITATIVE RENAL SCINTIGRAPHY

The feasibility and reproducibility of obtaining the pulsed-wave Doppler measurements of resistive index (RI) and pulsatility index (PI) were investigated in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with isoflurane. In addition, relative renal function and relative renal blood flow were evaluated using quantitative renal scintigraphy. The percentage of injected dose uptake, time to peak activity, and two indices of renal blood flow (K/A ratio and flow index) obtained during the first pass of ^99mTc-MAG₃, were determined for both awake and anesthetized cats. Results indicate that measuring RI and PI in nonsedated cats is readily accomplished and that the results are reproducible within an animal. Mean RI and PI values in the awake cats were 0.55 and 0.8, respectively. Significant differences between the awake and anesthetized cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic measurements evaluated.