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.     

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.     

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.     

TRANSSPLENIC PORTAL SCINTIGRAPHY USING 99MTC-MEBROFENIN IN NORMAL DOGS

Transsplenic portal scintigraphy using sodium pertechnetate is superior to per-rectal portal scintigraphy due to improved visualization of the portal vasculature with decreased patient and personnel exposure. The purpose of this study was to describe the use of 99mTc-mebrofenin, the radiopharmaceutical of choice for the evaluation of hepatic function, in place of pertechnetate for transsplenic portal scintigraphy in normal dogs. Sixteen juvenile dogs underwent transsplenic portal scintigraphy using 37-130 MBq 99mTc-mebrofenin in a 0.2-0.5 ml volume. After the initial dynamic acquisition obtained at 4 frames/s in right lateral recumbency, static right lateral, and ventral views were obtained at 5, 10, 15, 20, 25, 30, 40, 50, and 60 min. A nuclear angiogram of the splenic and portal veins was visible in all dogs, followed by rapid distribution of the radiopharmaceutical in the liver. Hepatic morphology was more easily defined than with pertechnetate. Transit time could not be calculated due to the high hepatic extraction of 99mTc-mebrofenin. Mean +/- SD shunt fraction was 0.8 +/- 0.8%. Time to peak liver activity was 3.1 +/- 1.1 min, and hepatic excretion T1/2 was 19.4 +/- 6.3 min. No visible blood pool and cardiac activity was seen after 5 min. The mean +/- SD time to visualization of defined biliary activity was 8.8 +/- 2.9 min. Absorption from the spleen was significantly higher than that reported for pertechnetate (87.9 +/- 8.2%, vs. 52.5 +/- 19.1%). 99mTc-mebrofenin can be used in place of pertechnetate for transsplenic portal scintigraphy, with the advantage of combining quantitative parameters of liver function with the already known advantage of transsplenic portal scintigraphy.     

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

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

EVALUATION OF HEART TIME-ACTIVITY CURVES AS A PREDICTOR OF HEPATIC EXTRACTION OF 99mTc-MEBROFENIN IN DOGS

In this study, heart time-activity curve, created following intravenous injection of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and dogs with induced hepatic parenchymal cell damage. The results were compared to a direct measurement of hepatic extraction following mesenteric venous injection of 99mTc-mebrofenin. The heart time-activity curves were normalized and the area under the curve from 0-30 minutes and 0-60 minutes were determined. In addition, the half-time clearance rate of the heart time-activity curve was analyzed using a two-compartment model. Linear regression analysis was used to describe the relationship between the area under the normalized heart time-activity curve and hepatic extraction. There was good correlation between the area under the normalized heart time-activity curve and hepatic extraction. The best correlation was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating hepatic extraction was derived using linear regression analysis: Hepatic extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation between the half-time clearance rates from the heart time-activity curve and hepatic extraction. The best correlation was between the fast phase half-time clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart time-activity curve can be used as a simple alternative to deconvolutional analysis for the determination of hepatic extraction as a measure of hepatic parenchymal cell function in the dog.     

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 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.     

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.     

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.     

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.     

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.     

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.     

AN INFECTED HIP PROSTHESIS IN A DOG DIAGNOSED WITH A 99mTC-CIPROFLOXACIN (INFECTON) SCAN

This case report describes the use of the 99mTc-labeled radiopharmaceutical ciprofloxacin (Infecton) in a case of hip prosthesis loosening in a dog. Serial planar radiographs were not conclusive, and culture of the synovial fluid was negative. Antibiotic treatment did not result in improvement of the lameness. Scintigraphy was performed with 99-Tc-Infecton, a tracer claimed to be specific for infection. Antibiotic treatment was interrupted 6 weeks prior to the examination. Planar and tomographic images at 3 h and at 24 h postinjection showed increased activity along the acetabulum and the proximal femoral bone surrounding the femoral prosthesis, indicating focal infection. Bacteriology performed after removal of the implant revealed Pseudomonas aeruginosa.     

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.     

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.     

99mTc-MDP COMBINED BLOOD POOL AND BONE PHASE RADIONUCLIDE IMAGING IN PAPAIN-INJECTED CARPAL JOINTS

Scintigraphic changes, i.e. , increased activity, were induced by 1% papain, dissolved in phosphate-buffered physiologic saline (pH 7.4), injected into one antebrachiocarpal joint in each of eight dogs. Scintigraphic evaluation was by the use of combined blood pool and bone phase scintigraphy of affected and normal carpi over a 28-day period. The qualitative and quantitative scintigraphic appearance in injected carpal joints were very similar in both blood pool and bone phases. The clinical use of combined blood pool and bone phase scintigraphy to diagnose early inflammatory joint changes appears limited.     

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.     

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.     

ULTRASONOGRAPHIC APPEARANCE OF THE INTRAVASCULAR TRANSIT OF AGITATED SALINE IN NORMAL DOGS FOLLOWING ULTRASOUND GUIDED PERCUTANEOUS SPLENIC INJECTION

Portosystemic shunts (PSSs) allow portal blood to bypass the liver and enter the systemic circulation. Definitive diagnosis requires surgical identification, positive contrast portography, ultrasonography, or scintigraphy. This study was designed as a preliminary step to developing an alternative/adjuvant protocol to these imaging modalities. The main goals were to establish a technique for ultrasound‐guided percutaneous trans‐splenic injection of agitated saline, to evaluate the feasibility of performing the test to explore the postsplenic portal vasculature highlighted by the microbubbles, and to ascertain whether agitated saline microbubbles cross the sinusoidal barrier. Agitated saline was injected into the spleen of 20 healthy sedated dogs under sonographic guidance. The transducer was then repositioned to visualize the portal vein, the caudal vena cava, and the right atrium through different acoustic windows. Satisfactory results were achieved in all dogs. The microbubbles were visualized in all dogs as small intense echo signals within the portal vein at the level of the porta hepatis immediately after injection. In 18 out of 20 dogs, the echogenic signal of the microbubbles disappeared immediately once within the hepatic parenchyma, whereas in two dogs, the echoes from the microbubbles lasted for several seconds within the intrahepatic portal vasculature. The absence of microbubbles beyond the sinusoidal barrier in all of the healthy dogs included in this study makes trans‐splenic injection of agitated saline a candidate as an adjuvant technique for the diagnosis of PSS, being easy to perform and repeat, as well as safe and technically feasible.