PRELIMINARY EVALUATION OF 99mTECHNETIUM DIETHYLENETRIAMINE PENTAACETIC ACID, 99mTECHNETIUM DIMERCAPTOSUCCINIC ACID, AND 99mTECHNETIUM MERCAPTOACETYLTRIGLYCINE FOR RENAL SCINTIGRAPHY IN CORN SNAKES (ELAPHE GUTTATA GUTTATA)

The efficacy of three radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), for renal imaging was examined in 16 corn snakes (Elaphe guttata guttata). All snakes received the radiopharmaceutical via an intracardiac injection. The kidneys could not be visualized in the three snakes that received 99mTc-DTPA or in the three snakes that received 99mTc-DMSA, but were well delineated in all 10 snakes receiving 99mTc-MAG3. These snakes were anesthetized and a dynamic frame mode acquisition was obtained for 30 min immediately following injection. A 60 s single static frame mode image was then obtained with the snake in a curled position. Two of the 10 snakes that received 99mTc-MAG3 were removed from further analysis because of suspected pericardial injections. Of the remaining eight snakes, the mean (+/- SD) renal uptake was 25 +/- 9.8% or 24 +/- 9.7%, with or without correction for residual injection site activity, respectively. Correction for remaining radioactivity in the heart does not appear to be necessary if it is less than 10% of the total dose. 99mTc-MAG3 provided consistently high quality images of the kidneys and further studies are warranted to evaluate its sensitivity for detecting decreased function in snakes with renal disease.     

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.     

THE EFFECTS OF A UNILATERAL ULTRASOUND-GUIDED RENAL BIOPSY ON RENAL FUNCTION IN HEALTHY SEDATED CATS

Complications of renal biopsies are well documented except for the change in renal function after a biopsy. Eighteen healthy, adult cats were divided into two groups (n = 9 cats/group). For the measurement of global and split renal function, Group 1 used the renal uptake of 99mTc-DTPA and Group 2 used the renal uptake of 99mTc-MAG3. Scintigraphic data were collected on days (-4), (-3), 0, 1, 2, and 4 post renal biopsy. Using ultrasound guidance, biopsies were taken from the right renal cortex on dO, before acquiring scintigraphic images. P - values less than 0.10 were considered significant due to the limited number of observations. The only statistically significant change (p = 0.08) in global renal function detected was by day following a unilateral renal biopsy. Cats imaged using 99mTc-MAG3 had discernible liver activity. A unilateral, ultrasound guided renal biopsy has minimal effect on renal function in normal, healthy sedated cats.     

EFFECTS OF ACEPROMAZINE ON THREE-PHASE 99mTc-MDP BONE IMAGING IN 11 HORSES

Horses undergoing skeletal scintigraphy can have decreased radiopharmaceutical bone uptake in the limbs. This reduces the diagnostic value of the scan. The aim of the present study was to measure the changes in count density caused by vasodilatation and increased blood flow associated with intravenous injection of acepromazine during bone scintigraphy in normal horses. A three-phase bone scan was performed twice in 11 adult horses to study the effects of acepromazine on the count density of the resultant scintigrams. With acepromazine, there was a statistically significant mean difference of 12 s for initial blood flow and 21 s for peak flow. The time to initial blood flow and time to peak flow occurred earlier for the scans in which acepromazine was used. There were no significant differences in the bone to soft tissue ratios during the soft tissue and bone phases of the scan between procedures. Intravenous administration of acepromazine increases peripheral blood flow causing an earlier onset of the vascular phase during the three-phase bone scan. Acepromazine did not increase the count density of the bone phase scintigrams. As expected, the vasodilatation and increased blood flow associated with intravenous injection of acepromazine affected the count density of the vascular phase of the bone scan.     

SCINTIGRAPHIC PATTERN OF 99mTc–MDP UPTAKE IN EXERCISE INDUCED PROXIMAL PHALANGEAL TRAUMA IN HORSES

Sixty–nine horses having radionuclide bone scans of the foredigit region between 1985 and 1988 were retrospectively analyzed for proximal phalangeal cortical ^99mTc–MDP uptake. Patterns of uptake were determined and the factors of age, breed, sex, occupation, and duration of signs prior to imaging were assessed. Twenty–three horses had abnormal proximal phalangeal uptake. Two patterns of uptake were seen, either as linear, diffuse or focal, discrete, fusiform–shaped cortical uptake. The dorsal cortex was always affected in these 23 horses; the palmar cortex was affected in 14 horses, and this uptake was always linear in appearance. There was significant correlation of proximal phalangeal cortical uptake and regular jumping activity, either as a jumping, hunting or three–day event horse ( p < .005). No correlations were determined between uptake and the factors of age, breed, sex or duration of signs prior to imaging. The scintigraphic appearance patterns were similar to those seen in scintigraphic studies of exercise induced traumatic bone injuries in humans.     

CLINICAL USE OF 99mTC-MDP SCINTIGRAPHY IN THE EQUINE MANDIBLE AND MAXILLA

^99mTc-methylene diphosphonate (MDP) radionuclide imaging examinations were done in four horses having clinical evidence of skull trauma or infection. Radiographs were made of each horse prior to scintigraphy. Four case histories are presented. In each instance, scintigraphy provided complementary information to that obtainable through radiography, which aided in accurately localizing and characterizing the site and extent of abnormalities, and which proved particularly valuable as an aid for therapeutic planning.     

THE APPLICATION OF TECHNETIUM-99m HEXAMETHYLPROPYLENEAMINE OXIME (99mTc-HMPAO) LABELED WHITE BLOOD CELLS FOR THE DIAGNOSIS OF RIGHT DORSAL ULCERATIVE COLITIS IN TWO HORSES

The application of 99mTc-HMPAO labeled white blood cells to support the diagnosis of right dorsal ulcerative colitis was studied in two horses with a history and clinical signs consistent with phenylbutazone toxicity. These images were compared to a reference horse unaffected by right dorsal ulcerative colitis. Blood was collected aseptically in heparinized syringes from the patients for in vitro white blood cell (WBC) radiolabeling. The buffy coat was separated out and radiolabeled with 99mTc-HMPAO. The radiolabeled blood was re-injected i.v. and four images of the right and left side of the patient's abdomen were acquired at 4 hours and 20 hours post-injection. Results of the nuclear study revealed no abnormal findings in the abdomen at the four-hour post-injection images in any horse. Images obtained 20 hours post-injection revealed a linear uptake of radiolabeled WBCs in the right cranioventral abdomen in the region of the right dorsal colon in both horses with right dorsal ulcerative colitis. The reference horse had no radiopharmaceutical uptake in this region. This nuclear imaging study was a rapid, non-invasive method to identify right dorsal colon inflammation. These findings not only supported the diagnosis of right dorsal ulcerative colitis, but also facilitated appropriate medical management of each horse.     

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.     

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

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

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.     

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.     

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.     

RENAL TRANSIT TIME OF 99mTc-DIETHYLENETRIAMINEPENTACETIC ACID (DTPA) IN NORMAL DOGS

The transit time of 99mTc-DTPA in the kidneys is an indicator of renal function that has been used in humans for the diagnosis of renal obstruction, renal artery stenosis, and rejection of renal transplants. Its use, however, has not been reported in the dog. 99mTc-DTPA scintigraphy was performed in 8 normal dogs and the time of peak was calculated as the time between the injection and the maximum renal uptake. Deconvolution analysis was performed to estimate the renal retention function using 3 different techniques, i.e. the matrix method, the fast Fourier transform (FFT) method, and the constrained least square method. The parenchymal and whole kidney mean transit times were calculated from the deconvolved renogram using alternatively the thorax and the aorta as the input function. Average mean transit times ranged from 137 to 184 seconds. Parenchymal mean transit time was significantly shorter than whole kidney mean transit time (P<0.03). Mean transit time calculated with the thorax as the input function was significantly longer than mean transit time calculated with the aorta (P<0.001). No differences were observed between mean transit time calculated with the matrix, FFT and constrained least square methods.     

EVALUATION OF LYMPHOMA IN A CAT USING 99mTc-SESTAMIBI

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

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.     

USE OF FIRST-PASS NUCLEAR ANGIOCARDIOGRAPHY TO DETECT LEFT-TO-RIGHT CARDIAC SHUNTS IN THE HORSE

First-pass nuclear angiocardiography was performed on 13 normal horses and 5 horses with confirmed left-to-right ventricular septal defects. Two methods of analyzing the ensuing pulmonary time-activity histograms for shunt recirculation through the lungs were evaluated: (1) pulmonary-to-systemic blood flow ratio (QP:QS), based on gamma variate modeling of the lung histogram, and (2) a simple count-ratio method (C2:C1). Normal values were QP:QS=1.17±0.04 and C2:C1=0.40±0.07. Values for the five horses with left-to-right shunts were QP:QS=2.94±0.13 and C2:C1=0.76±0.11. Both parameters showed significant differences (unpaired t -test; p <0.005) between the two groups, although separation was better with QP:QS.     

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.     

Diagnosis of Congenital Cardiac Right-to-left Shunts with 99mTc-macroaggregated Albumin

Diagnosing right-to-left congenital cardiac shunts can be difficult. Cardiac catheterization and angiocardiography represent the traditional gold standard for diagnosis, but they are invasive. Nuclear scintigraphy using 99mTc-macroaggregated albumin (MAA) has been employed in humans as an alternate method of diagnosis. This study reviews eight dogs presented for evaluation of a suspect right-to-left cardiac shunt that were examined using 99mTc-MAA. In all, 2-4 mCi (74-148 MBq) of reduced particle 99mTc-MAA were injected IV in a cephalic vein and static images of the whole body, including right and left lateral, dorsal, and ventral views, were acquired for 60 s and stored into a 256 x 256 x 16 matrix. Shunt fractions were calculated. One dog with radiopharmaceutical distribution limited to the lungs did not have a shunt. Seven dogs had distribution of the radiopharmaceutical outside the pulmonary capillary bed, indicating bypassing of the pulmonary capillary circulation due to a right-to-left shunt. Four dogs had 99mTc-MAA within the brain. Three dogs that did not have brain uptake, but instead had a sharp cutoff of radioactivity at the level of the front limbs and neck, were diagnosed with reverse patent ductus arteriosus (PDA). The asymmetric distribution of the radiopharmaceutical is due to the location of the shunt, distal to the brachiocephalic trunk and left subclavian artery. Shunt fractions of dogs with extrapulmonary radioactivity ranged from 40% to 59%. Nuclear scintigraphy with 99mTc-MAA is a quick alternative method of diagnosing right-to-left cardiac shunts that permits quantification of shunt fraction. Distinguishing between reverse PDA and other right-to-left shunts may be possible based on the radiopharmaceutical distribution.     

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.     

EFFECT OF REGION OF INTEREST SELECTION AND UPTAKE MEASUREMENT ON GLOMERULAR FILTRATION RATE MEASURED BY 99mTc-DTPA SCINTIGRAPHY IN DOGS

Determinations of different methods of measurement of uptake of 99mTc-DTPA using scintigraphy of glomerular filtration rate (GFR) were made from 29 studies on 10 healthy beagle dogs. GFR was measured by calculating the percentage dose uptake (integral method) and rate of uptake (slope method) of 99mTc-DTPA using manual kidney regions of interest (ROI) and automatic kidney and background ROIs at different time periods of the uptake phase. These results were compared using linear regression analysis to the GFR obtained from 99mTc-DTPA plasma clearance using multiple blood samples. The best correlation coefficient between percentage DTPA uptake and GFR by DTPA clearance (r = 0.84, P < 0.001) was derived from time intervals between 30s-120s with a perirenal background ROI at 1 or 2 pixels out from the kidney ROI using automatic kidney ROI at 20% threshold. With the slope method, the best correlation coefficient (r = 0.85, P < 0.001) was obtained from time intervals between 30s-peak with the background ROI at 2 pixels out from the kidney ROI using automatic ROI at 35% threshold. The offset was higher, and the correlation varied more with different ROIs and the method was unreliable at time intervals extending beyond the peak radioactivity. Manual kidney ROIs with automatic background ROIs had slightly lower correlations. With DTPA renography both integral and slope uptake method with automatic kidney and background ROIs are accurate methods to estimate the GFR, but that the integral method is much more stable to variations in ROI size and the duration of the uptake phase of the renogram.