Variable bile retention on cholescintigraphy after morphine administration

Intravenous morphine sulfate has been used in conjunction with cholescintigraphy. We studied the variations in the degree and duration of the effects of 2 mg morphine on biliary kinetics in patients with gallbladder nonvisualization and undertook a comparison with biliary kinetics in patients not given morphine. Of 24 morphine-augmented cholescintigrams that were obtained without additional injection of technetium-99m diisopropyl-iminodiacetic acid (DISIDA), 19 showed continued gallbladder nonvisualization. Time-activity curves (TACs) of the liver parenchyma and common bile/hepatic duct (CD) of the entire study (before and after morphine) were obtained. In two patients, the CD was not sufficiently visualized to define a region of interest. In 17 patients, the peak CD activity was observed between 14 and 47 min after injection of^99mTc-DISIDA. In these 17, the TAC of the CD was declining essentially in parallel with the TAC of the liver parenchyma at the end of the first hour before morphine. After morphine injection, CD activity slowly increased for a variable duration in nine patients, while it continued to decrease in eight. CD activity between 1 h and 2 h showed a continuously decreasing pattern in another group of 20 patients who did not receive morphine despite gallbladder nonvisualization at 1 h. In summary, no significant effect of 2 mg of intravenous morphine on biliary kinetics was detected scintigraphically in a considerable proportion of patients. Also, there was considerable variation in the duration of the effect of morphine, when such an effect was present. This observation may have significant clinical implications for morphine-augmented cholescintigraphy.     

Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model

Purpose This study evaluated the utility of non-invasive assessment of hepatobiliary function by ^99mTc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis.Methods Male Wistar rats (250–300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. ^99mTc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T _peak) and the time required for peak activity to decrease by 50% (T _1/2peak). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology.Results MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T _peak, T _1/2peak prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p<0.05). There was a strong, significant correlation between the severity of steatosis (histopathology, hepatic triglyceride content) and the ^99mTc-mebrofenin uptake rate (r ²=0.83, p<0.0001 and r ²=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-α, r ²=0.72, p<0.0001 and r ²=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r ²=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r ²=0.70, p<0.001).Conclusion Hepatobiliary function assessed by ^99mTc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients.     

Evaluation of common bile duct stenosis in chronic pancreatitis using cholescintigraphy

To evaluate a stenotic change of the common bile duct (CBD) in chronic pancreatitis (CP), cholescintigraphy with ^99mTc-N-pyridoxyl-5-methyltryptophan (PMT) was performed in 28 patients with CP and 15 normal subjects. The patients were divided into 3 groups on the basis of their endoscopic retrograde cholangiopancreatography (ERCP) findings: minimal CP (MIP; n=14), moderate CP (MOP; n=10), and advanced CP (ADP; n=4). After intravenous injection of 5 mCi ^99mTc-PMT, digital images were obtained and time activity curves of the ROIs (liver, hepatic duct, gallbladder, and duodenum) were generated. No radioactivity was seen in the duodenum within 1 hour in 12 of 28 (43%) with CP and 2 of 15 (13%) normals. Reflux to the hepatic duct after cerulein injection was found in 6 of 20 (30%) examined patients with CP and more frequently in ADP, whereas there was no reflux in MIP and normals. When the finding of reflux in cholescintigraphy was interpreted as positive for CBD stenosis, the sensitivity, specificity, and accuracy were 100%, 88%, and 90%, respectively. We conlcude that reflux is a reliable scintigraphic finding in detecting CBD stenosis.     

Uptake of Tc tetrofosmin in lymphoma cell lines: a comparative study with Tc sestamibi

Technetium-99m (^99mTc) tetrofosmin has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of ^99mTc tetrofosmin in lymphoma cell lines. ^99mTc sestamibi was also evaluated for comparison. Three lymphoma cell lines (U-937: monocyte-like, histiocytic lymphoma, human; RAMOS: B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hs445: Hodgkin's disease, lymphoid, human) were studied. After incubation of radiotracers ^99mTc tetrofosmin and ^99mTc sestamibi in medium for 0, 10, 20, 30, 60, 120 and 180 min, the uptake and clearance of each radiotracer were measured in the three lymphoma cell lines. The uptake of ^99mTc tetrofosmin was lower than that of ^99mTc sestamibi in these lymphoma cell lines. Among the three cell lines, Hs445 showed the greatest ^99mTc tetrofosmin uptake capacity. RAMOS and U-937 showed similar ^99mTc tetrofosmin uptake capacities. ^99mTc tetrofosmin accumulated in the three tested lymphoma cell lines, especially in the Hodgkin's disease cell line. However, in comparison with ^99mTc sestamibi, ^99mTc tetrofosmin may not be the best radiotracer for detection of lymphoma.     

Usefulness of fatty meal-stimulated cholescintigraphy in the diagnosis and treatment of chronic acalculous cholecystitis

Objective  Fatty meal cholescintigraphy (fatty meal CS) is a potential physiologic alternative for cholecystokinin (CCK) CS in the diagnosis and treatment of chronic acalculous cholecystitis (CAC). However, there are limited data in the literature to support this assumption. Our objective was to determine the usefulness of fatty meal CS in the diagnosis and treatment of CAC. Methods  We retrospectively reviewed the medical records of 198 patients who had undergone fatty meal CS for presumed CAC. Data retrieved focused on symptom improvement following management. Gallbladder ejection fraction (GBEF) of 50% or less was considered abnormal. Patients were divided into groups on the basis of test results and management. Results  In group 1a, patients with low GBEF and cholecystectomy, 88% (54 of 61) reported symptom improvement, whereas the remaining 12% (7 of 61) retained their symptoms. Group 1b consisted of patients with low GBEF and who were managed medically. Persistence of symptoms was noted in 76% (32 of 42) of patients, whereas the remaining 24% (10 of 42) had symptom improvement. Group 2 consisted of patients with normal GBEF. Follow-up showed that 60% (47 of 78) of patients had symptom improvement either spontaneously or on medical treatment, whereas the remaining 40% (31 of 78) retained their symptoms. Conclusions  Fatty meal CS is a very useful technique in the diagnosis of CAC. It predicts a good surgical outcome once GBEF is low in patients with high pre-test probability for CAC. Moreover, fatty meal CS may be a good alternative to CCK CS.     

Contribution of cholescintigraphy to the early diagnosis of acute acalculous cholecystitis in intensive-care-unit patients

Thirty-two intensive care unit patients (78% on long-term total parenteral nutrition) suspected of having acute acalculous cholecystitis (AAC) were studied prospectively. All of these patients underwent abdominal ultrasonography and cholescintigraphy with technetium-99m mebrofenin. Morphine sulphate (0.04 mg/kg) was administered only if the gallbladder was not visualised after 1 h (16 patients). The final diagnosis was reached after clinical improvement, or upon the discovery of another aetiology for the symptoms presented, or on the basis of histopathology following cholecystectomy (when this was performed). We analysed the contribution of individual cholescintigraphic findings (I: non-visualisation of the gallbladder during the first 60 min of the examination; II: persistent non-visualisation of the gallbladder 30 min following morphine administration; III: non-visualisation of the small bowel for at least 90 min) and their various combinations. We obtained a sensitivity of 79% and a specificity rate 100% using the interpretative criteria ”I and II or III”. Excluding obstructive syndrome (”I and II”), the sensitivity and specificity figures were 70% and 100% respectively (28 patients). We had no false-positive results in our patient population. Cholescintigraphy was found to complement ultrasonography, which had either good sensitivity (93%) and poor specificity (17%), when at least two of the three major signs were present (sludge, thickened wall, gallbladder distension), or poor sensitivity (36%) and good specificity (89%) when all three signs were present. We conclude that cholescintigraphy is a useful tool for early diagnosis of AAC in critically ill patients, in whom ultrasonography alone does not provide enough information to permit a sufficiently early decision regarding the use of surgery. Received 1 April and in revised form 1 June 1999     

99mTc-抗D-二聚体单抗对实验动物陈旧性血栓的放射免疫显像研究

目的研究^99Tc标记的抗D-二聚体单抗在陈旧性动脉血栓和静脉血栓靶向定位诊断中的应用。方法采用机械损伤血管内膜的方法复制家兔股动脉血栓和股静脉血栓模型，血栓形成后3d将^99Tc标记的抗D-二聚体单抗注入动物血管内，以放射免疫显像检测技术观察放射性核素在血流和血栓部位的分布。结果血栓处放射性^99Tc的分布较健侧明显增多，而单纯钳夹血管组及正常对照组未见局部放射性物质的堆积。注入^99Tc标记的单抗后，动物未见不良反应，主要脏器未见病理改变。结论^99Tc标记的抗D-二聚体单抗可以作为血栓导向示踪剂，用于陈旧性动脉血栓和静脉血栓的定位诊断。     

Novel Tcradiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with ^99mTc was greater than 98% and the complex was stable for about 7 hours at 37°C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of ^99mTc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that ^99mTc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.     

Iodinated cholylglycyltyrosine: A new agent for hepatobiliary imaging

The characteristics of radiolabelled cholylglycyl-tyrosine (CGT), a recently synthesised bile acid, were studied. ¹²⁵I-CGT-Na was found to have a short plasma half-life of 1.6±0.4 min in rats and 3.1±0.7 min in dogs. Biliary clearance studies showed the cumulative biliary output of the tracer over 20 min in rats to be 95.7% of the total dose administered, with a mean biliary transit time (50% retention time) of 4.0±0.1 min, i.e. similar to the biliary kinetics of taurocholate. ¹³¹I-CGT-Na proved to be satisfactory for hepatobiliary imaging in rats and dogs at doses of 35 Ci (1.3 MBq) in rats and 90 Ci (3.3 MBq) in dogs. Satisfactory hepatic images were also obtained in rats that had high bilirubin levels produced by obstruction or the recycling of bile. These results show that CGT has better pharmacokinetics than currently used hepatobiliary imaging agents, and that this new compound may be useful in scintigraphy even in the presence of jaundice.     

Comparison of dynamic MR imaging of the breast and sestamibi scintimammography for evaluation of indeterminate mammographic lesions

The aim of this study was to compare Tc-99m sestamibi scintimammography and dynamic contrast-enhanced MR imaging for the evaluation of indeterminate mammographic lesions. Forty patients with questionable mammographic findings were included in a prospective study. Thirty lesions were non-palpable. Mean lesion size was 1.6+/-0.7 cm (range 0.5-3.5 cm). Scintigraphy was considered as malignant when focal tracer accumulation was present. In MR imaging, lesions were classified according to their signal intensity time course: no enhancement or steady enhancement with low signal intensity (M0); steady enhancement with high signal intensity (M1); or rapid enhancement with plateau (M2) or washout (M3). Lesions classified as M2 or M3 were considered as suspicious for malignancy. Histopathologic evaluation was performed in 24 lesions. In 16 cases lesions were classified as benign from follow-up examinations (mean 24 months). Malignancies were proven in 14 patients (9 invasive carcinomas, 5 ductal carcinoma in situ). Sensitivity of MR imaging was 12 of 14 (86%) and sensitivity of scintimammography was 8 of 14 (57%). One of 26 benign lesions was false positive at MR imaging. Scintigraphy showed no false-positive results. In conclusion, magnetic resonance imaging provided high accuracy in evaluation of indeterminate mammographic lesions. Sensitivity of scintimammography was too low in detecting small carcinomas.     

Biodistribution studies of Tc-labeled myoblasts in a murine model of muscular dystrophy

The purpose of this study was twofold: first, to evaluate the myoblast labeling of various ^99mTc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne’s muscular dystrophy). The following ligands were used to prepare the corresponding ^99mTc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt).

One million murine myoblasts were incubated for 30–60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [^99mTc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin.     

Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.     

Pulmonary scintigraphy with a triple-head camera for evaluation of acute pulmonary embolism

Ventilation-perfusion scintigraphy is a useful test for the evaluation of acute pulmonary embolism. While the sensitivity is high, there is concern from the PIOPED experience about potentially suboptimal specificity, in part reflected by a 39 % rate of intermediate probability lung scans as reported by the PIOPED investigators [7]. To help address this concern, we developed a modified procedure for ventilation scintigraphy with xenon-133 in which two serial dynamic ventilation studies offset by 180 ° were acquired with a triple-head gamma camera, yielding a six-view assessment of pulmonary ventilation. This was followed by a six-view acquisition of pulmonary perfusion with technetium-99m-macroaggregated albumin (MAA) using the same camera. A series of 100 scintigraphic assessments incorporating this procedure to evaluate possible acute pulmonary embolism were systematically reviewed to assess the potential interpretive merits of the additional ventilation views, compared to the traditional single posterior xenon-133 ventilation view. There were 36 cases identified for which the additional ventilation views were graded as either “somewhat helpful” or “essential” in formulating the scan interpretation. Of the 36 cases, 26 (72 %) were in the “low” and “high” probability categories, thereby helping to reduce the proportion of intermediate probability scan results to only 16/100, less than half the rate observed in the PIOPED experience. Thus, the use of this modified scintigraphic procedure allows multiview ventilation-perfusion assessment with xenon-133 as the ventilation tracer, improves interpretability of the scans, and helps to increase the proportion of definitive assessments for the evaluation of acute pulmonary embolism.     

Preparation and evaluation of 99mTc(V)-DMSA complex: Studies in medullary carcinoma of thyroid

Consequent to the promising results reported with ^99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways:-(i) from freshly prepared reagents, (ii) through the use of a two component kit and (iii) use of the standard renal DMSA kit by a modified recipe. The ^99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

Technetium-99m HYNIC-annexin V: a potential radiopharmaceutical for the in-vivo detection of apoptosis

Either inadequate or excessive apoptosis (programmed cell death) is associated with many diseases. A method to image apoptosis in vivo, rather than requiring histologic evaluation of tissue, could assist with therapeutic decision making in these disorders. Programmed cell death is associated with a well-choreographed series of events resulting in the cessation of normal cell function, and the ultimate disappearance of the cell. One component of apoptosis is signaling adjacent cells that this cell is committing suicide by externalizing phosphatidylserine to the outer leaflet of the cell membrane. Annexin V, a 32-kDa endogenous human protein, has a high affinity for membrane-bound phosphatidylserine. We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo. In this report we describe the results of a series of experiments in mice and rats to characterize the biologic behavior of ^99mTc-HYNIC- annexin V. Biodistribution studies were performed in groups of rats at 10–180 min after intravenous injection of ^99mTc-HYNIC-annexin V. In order to estimate the degree of apoptosis required for localization of ^99mTc-annexin V in vivo, mice were treated with dexamethasone at doses ranging from 1 to 20 mg/kg, 5 h prior to ^99mTc-HYNIC-annexin V administration, to induce thymic apoptosis. Thymus was excised 1 h after radiolabeled HYNIC-annexin V injection; thymocytes were isolated, incubated with Hoechst 33342 followed by propidium iodide, and analyzed on a fluorescence-activated cell sorter. Each sorted cell population was counted in a scintillation counter. To test ^99mTc-HYNIC-annexin V as a tracer for external radionuclide imaging of apoptotic cell death, radionuclide imaging of Fas-defective mice (lpr/lpr mice) and wild-type mice treated with the antibody to Fas (anti-Fas) was carried out 1 h post injection. Rat biodistribution studies demonstrated a blood clearance half-time of less than 10 min for ^99mTc-HYNIC-annexin V. The kidneys had the highest concentration of radioactivity at all time points. Studies in the mouse thymus demonstrated a 40-fold increase in ^99mTc-HYNIC-annexin V concentration in apoptotic thymocytes compared with the viable cell population. A correlation of r=0.78 was found between radioactivity and flow cytometric and histologic evidence of apoptosis. Imaging studies in the lpr/lpr and wild-type mice showed a substantial increase of activity in the liver of wild-type mice treated with anti-Fas, while there was no significant change, irrespective of anti-Fas administration, in lpr/lpr mice. Excellent images of hepatic apoptosis were obtained in wild-type mice 30 min after injection of ^99mTc-HYNIC-annexin V. The imaging results were consistent with histologic analysis in these animals. In conlusion, these studies confirm the value of ^99mTc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo. Received 22 February and in revised from 5 May 1999     

Formulation of a single-component kit for the preparation of technetium-99m labelled ethyl cysteinate dimer: biological and clinical evaluation

Ethyl cysteinate dimer (ECD) labelled with reduced technetium-99m has recently been proposed as a promising radiopharmaceutical for brain perfusion imaging. In the present study a single-component kit formulation has been developed, thus simplifying the radiolabelling procedure. A method of analysis by electrophoresis has also been developed, permitting identification of radiochemical impurities in the preparation. ^99mTc-ECD prepared by the single-component kit was further evaluated in primates and humans. The results demonstrated that the complex is stable in vivo, rapidly extracted and retained in the brain tissue for a sufficient time for single-photon emission tomography studies. Therefore the present single-component kit formulation can be proposed as a reliable instant freeze-dried kit for routine preparation of 99-Tc-ECD required for scintigraphic assessment of regional cerebral blood flow.     

Radiosynthesis,molecular modeling studies and biological evaluation of 99mTc-Ifosfamide complex as a novel probe for solid tumor imaging

Purpose: Ifosfamide as a chemotherapeutic drug is used for the treatment of different cancer types. The purpose of this study is the preparation of ^99mTc-ifosfamide complex to be evaluated as a potential candidate for tumor imaging.

Materials and methods: The radiolabeling of ifosfamide with technetium-99m was carried out by mixing 4mg ifosfamide and 5?μg of SnCl₂.2H₂O with 400 MBq Na^99mTcO₄ at pH 9 for 30?min at room temperature. Computer simulation studies were performed using Accelrys Discovery Studio 2.5 operating system to illustrate the interaction of ifosfamide and ^99mTc-ifosfamide complexes with DNA. The in-vivo biodistribution of ^99mTc-ifosfamide was studied in tumor-bearing Albino mice.

Results: A new ^99mTc-ifosfamide complex was synthesized with a good radiochemical yield of 90.3?±?2.1% under the optimized conditions and exhibited in-vitro stability up to 2?h. Biodistribution studies showed good uptake in tumor site and high uptake in tumor site with T/NT ～3 after 60?min post-injection. Besides, the molecular docking study confirmed that the complexation of ifosfamide with technetium-99m does not abolish its binding to the target receptor.

Conclusion: These promising results afford a new radiopharmaceutical that could be used as a potential tumor imaging     

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. ^99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO₃ solution in the presence of a small amout of reducing agent (SnCl₂). On the other hand, trivalent ^99mTc-DMSA [^99m-Tc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only ^99mTc(V)-DMSA revealed an area of intense accumulation.