Initial results of the use of a novel semiquantitative parameter in three-phase bone scan to predict 99mTc-HMPAO-labeled leukocyte scintigraphy in patients with unilateral total knee replacement.

OBJECTIVES: The aim of the study was to predict the results of 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous leukocytes scintigraphy assessing count ratios in the perfusion (Pr) and blood-pool (BPr) phase images in three-phase bone scan (3PBSr) between the prosthetic knee and the 'healthy' knee and a novel semiquantitative parameter (P/BP ratio) in patients with unilateral knee arthroplasty. METHODS: Patients with unilateral knee arthroplasty and available 3PBS and 99mTc-HMPAO-labeled autologous leukocytes scintigraphic images were searched in two hospitals (A and B). In center A, the perfusion phase was not available. Regions of interest (ROI) were delineated in the perfusion (P) and blood-pool (BP) phase images, incorporating the prosthetic region and applying an isocontour (40% of the maximum pixel activity); corresponding mirror ROIs were placed on the healthy knee. The P/BP ratio was calculated as {[(Pr/BPr) × 100] - 100}. Receiver operator curves (ROCs) were generated for each semiquantitative parameter to identify the optimal cutoff for predicting the results of the autologous leukocytes scintigraphy. RESULTS: In the whole group (79 patients), BPr demonstrated an area under the curve (AUC) of 0.722 (optimal cutoff = 1.43). In center A (52 patients), BPr demonstrated an AUC of 0.737 (cutoff = 1.43), whereas, in center B (27 patients), AUC for BPr was 0.718 (cutoff = 1.6). A better diagnostic performance was obtained selecting Pr (AUC = 0.918; cutoff = 2.34) and P/BP ratio (AUC = 0.947; cutoff = 26.5%) for the discrimination between septic and aseptic loosening. CONCLUSIONS: The novel P/BP ratio seems to be a promising semiquantitative parameter to predict septic loosening. These findings warrant confirmation in larger patient samples.

Scintigraphy with 99mTc-HMPAO labeled leukocytes is still an accurate and convenient tool to rule out suspected inflammatory bowel disease in children.

BACKGROUND: Abdominal pain is a common complaint in children and its differential diagnosis includes inflammatory bowel disease (IBD). The aim of the study was to assess the diagnostic accuracy of scintigraphy with 99mTechnetium Hexamethylpropyleneamine Oxime (99mTc-HMPAO) labeled leukocytes in children with suspected IBD. MATERIAL AND METHODS: Eighty-five children (age 12.4 ± 4.3 years, 47% boys) with suspected IBD based on clinical presentation, laboratory and ultrasound findings underwent scintigraphy with 99mTc-HMPAO labeled leukocytes. Abdominal scintigrams were acquired 40 min and 90 min post injection, and whole body scintigrams at 180 min. Scintigraphy was evaluated by two specialists in nuclear medicine. The results were compared with the final diagnosis established by endoscopy, histology, other imaging methods, and follow-up evaluated by an expert in pediatric gastroenterology. RESULTS: Scintigraphy results corresponded with the final diagnosis in 78 (91%) patients resulting in a sensitivity of 89% (95%CI 72 to 98%), specificity of 91% (95% CI 82 to 98%), and accuracy of 91% (95% CI 83 to 96%). The interobserver agreement was 0.82 (95% CI 0.75 to 0.88) and the radiation dose estimate was 4.2 ± 1.5 mSv. In 28 children (25 positives and 3 negatives on scintigraphy), the diagnosis of IBD was established by endoscopy, histology, MR enterography, or fluoroscopy. Five positive findings on scintigraphy were not confirmed by other methods or during follow-up. CONCLUSION: Scintigraphy with 99mTc-HMPAO labeled leukocytes in children with suspected IBD has high accuracy and offers a non-invasive option for detecting the presence of gastrointestinal inflammation. Scintigraphy is a powerful non-invasive decision-making tool in the management of suspected IBD that may spare a greater proportion of children of more invasive and demanding examinations.

The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99mTc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration.

The usefulness of SPECT-CT with radioisotope-labeled leukocytes in diagnosing lead-dependent infective endocarditis.

BACKGROUND: Lead-dependent infective endocarditis (LDIE) is a life-threatening complication of permanent transvenous cardiac pacing. According to the 2015 European Society of Cardiology (ECS) guidelines, the diagnosis of LDIE is based on the modified Duke criteria (MDC), while single-photon emission computed tomography with conventional computed tomography (SPECT-CT) with radioisotope-labeled leukocytes serves as an additional tool in difficult cases. The major challenge is to differentiate between true vegetation and a thrombus. OBJECTIVES: The aim of the study was to evaluate the usefulness of SPECT-CT with radioisotope-labeled leukocytes in diagnosing LDIE in patients with intracardiac masses (ICMs). MATERIAL AND METHODS: The prospective registry included 40 consecutive patients admitted with an ICM on the lead and suspicion of LDIE. The confirmation or rejection of the LDIE diagnosis was made according to an algorithm based on the MDC. The cohort was divided into 2 groups: patients with definite and possible LDIE diagnoses based on the MDC (the LDIE-positive group), and patients with negative LDIE diagnoses according to the MDC (the LDIE-negative group). All patients underwent SPECT-CT with radioisotope-labeled leukocytes. The diagnostic ability of SPECT-CT was compared to the gold standard MDC. RESULTS: The LDIE-positive group with diagnosis based on the MDC consisted of 19 patients (LDIE definite - 11; LDIE possible - 8). The LDIE diagnosis was rejected on the basis of the MDC in 21 patients. The SPECT-CT results were compared with the MDC results and showed 73.7% sensitivity, 81.0% specificity, 77.5% accuracy, 77.8% positive predictive value (PPV), 77.3% negative predictive value (NPV), likelihood ratio positive (LR+) 3.868, likelihood ratio negative (LR-) 0.325, and moderate agreement (κ = 0.548, p < 0.001). After the exclusion of 5 patients treated with antibiotics at the time of the SPECT-CT, LR+ and LRimproved to 5.250 and 0, respectively, and inter-test agreement amounted to almost perfect concordance (κ = 0.773, p < 0.001). CONCLUSIONS: Single-photon emission computed tomography with conventional CT with radioisotopelabeled leukocytes is a useful, efficient, single-step test for diagnosing LDIE.

Radiolabeling of Preformed Niosomes with [99mTc]: In Vitro Stability, Biodistribution, and In Vivo Performance.

Nanocarriers radiolabeled with [99mTc] can be used for diagnostic imaging and radionuclide therapy, as well as tracking their pharmacokinetic and biodistribution characteristics. Due to the advantages of niosomes as an ideal drug delivery system, in this study, the radiolabeling procedure of niosomes by [99mTc]-HMPAO complexes was investigated and optimized. Glutathione (GSH)-loaded niosomes were prepared using a thin-film hydration method. To label the niosomes with [99mTc], the preformed GSH-loaded niosomes were incubated with the [99mTc]-HMPAO complex and were characterized for particle size, size distribution, zeta potential, morphology, and radiolabeling efficiency (RE). The effects of GSH concentration, incubation time, incubation temperature, and niosomal composition on RE were investigated. The biodistribution profile and in vivo SPECT/CT imaging of the niosomes and free [99mTc]-HMPAO were also studied. Based on the results, all vesicles had nano-sized structure (160-235 nm) and negative surface charge. Among the different experimental conditions that were tested, including various incubation times, incubation temperatures, and GSH concentrations, the optimum condition that resulted in a RE of 92% was 200-mM GSH and 15-min incubation at 40°C. The in vitro release study in plasma showed that about 20% of radioactivity was released after 24 h, indicating an acceptable radiolabeling stability in plasma. The biodistribution of niosomes was clearly different from the free radiolabel. Niosomes carrying radionuclide were successfully used for tracking the in vivo disposition of these carriers and SPECT/CT imaging in rats. Furthermore, biodistribution studies in tumor-bearing mice revealed higher tumor accumulation of the niosomal formulation as compared with [99mTc]-HMPAO.

Experiences with 99mTc-HMPAO in a Diagnostic Pathway for Violent Patients with Schizophrenic Spectrum Disorders.

BACKGROUND AND OBJECTIVE: In a security ward we assessed the diagnostic contribution of single photon scintigraphy [SPECT] in our diagnostic pathway for patients with serious mental disease and a history of violence. METHODS: Twenty patients were examined between 2012 and 2015 and the findings compared to those in nine patients with the same diagnosis, but no history of violence. RESULTS: All violent patients had areas with reduced accumulation of 99mTc-HMPAO frontally and in the temporal lobe, in the non-violent group only two patients demonstrated these findings. CONCLUSION: Traditionally, low accumulation of the tracer in SPECT is related to reduced perfusion of brain tissue. We discuss our findings in the light of other possible pathophysiological mechanisms.

A retrospective analysis of the accuracy of radioactively labeled autologous leukocytes in patients with infected prosthetic joints.

BACKGROUND: Labeled leukocyte scintigraphy (LS) is considered a valuable tool in preoperative diagnosis of prosthetic joint infections (PJI). The aim of this study was to determine the accuracy of LS combined with bone marrow scintigraphy (BMS), as well as inflammation markers CRP and WBC, in detecting infection in patients with prosthetic joints. MATERIAL AND METHODS: This study included patients suspected of having PJI between January and September 2013 at the Vienna General Hospital who underwent imaging with 99mTc-HMPAO labeled autologous leukocytes and subsequent BMS. Diagnostic accuracy was assessed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 48 patients were included. The most common joint investigated was knee (25), followed by hip (9), shoulder (2), and elbow (1). Other parts of the body investigated included the femur (6), tibia (2), leg (2), and foot (1). The pathogens most frequently isolated included Staphylococcus epidermidis and Candida albicans. The sensitivity of LS was 60%, specificity 97%, PPV 86% and NPV 90%. Overall accuracy was calculated to be 90%. CONCLUSIONS: This study was able to demonstrate that 99mTc-HMPAO labeled autologous leukocytes in patients presenting with symptoms of PJI is accurate. In contrast, however, inflammation markers CRP and WBC are not accurate pre-diagnostic markers for PJI.

New synthesis route of active substance d,l-HMPAO for preparation Technetium Tc99m Exametazime.

BACKGROUND: Technetium Tc99m Exametazime (99mTc-HMPAO) is currently used as a radiopharmaceutical for determining regional cerebral blood flow and for the labelling of autologous leucocytes for infection and inflammation imaging. The HMPAO ligand exists in two diastereomeric forms: d,l and meso. Usually, the substance is obtained in low chemical yield in a time consuming procedure. Furthermore, the final product still contains some amounts of the meso-form. The aim of this study was to develop the efficient, reliable and fast method for isolation of the d,l-HMPAO, which would provide the ligand with high purity and free from the meso-diastereomer. MATERIAL AND METHODS: The mixture of the meso- and d,l-HMPAO was synthesized in two-steps by condensation of propanediamine with keto-oxime and the reduction of the obtained bisimine. The d- and l-enantiomers were separated individually directly from this mixture by repeated crystallizations from ethanol as their tartrate salts and pooled together in equal proportions. That substance was characterized for its identity and isomeric purity using IR, HPLC and GC methods. The meso-free d,l-HMPAO was used for the preparation of the radiopharmaceutical freeze-dried kit for technetium-99m radiolabelling. Quality assessment of obtained 99mTc-d,l-HMPAO complex was performed according to the current Ph.Eur. monograph 1925 and USP monograph - Technetium Tc99m Exametazime Injection. To verify its biological activity, the kit-prepared 99mTc-d,l-HMPAO has been used for the white blood cell (WBC) labelling. RESULTS: According to the proposed synthesis route the d,l-HMPAO was obtained with around 18-20% yield in the total time of 10 days. The ligand identity was confirmed and the HPLC analysis revealed more than 99% chemical purity. The undesired meso-form was not detected. Freeze dried kit formulation for 99mTc-labelling of d,l-HMPAO has been established and four batches of kits were manufactured. The radiochemical purity of 99mTc-d,l-HMPAO complex was high (> 95% of lipophilic technetium-99m exametazime). Brain uptake in rats reached 2.1 ± 0.3%. The in vitro labelling of WBC resulted in 68.3 ± 6.6% yield. CONCLUSION: A new synthesis method of d,l-HMPAO, drug substance for technetium-99m exametazime preparation has been developed.

Intraarticular and intravenous administration of 99MTc-HMPAO-labeled human mesenchymal stem cells (99MTC-AH-MSCS): In vivo imaging and biodistribution.

INTRODUCTION: Therapeutic application of intravenous administered (IV) human bone marrow-derived mesenchymal stem cells (ahMSCs) appears to have as main drawback the massive retention of cells in the lung parenchyma, questioning the suitability of this via of administration. Intraarticular administration (IAR) could be considered as an alternative route for therapy in degenerative and traumatic joint lesions. Our work is outlined as a comparative study of biodistribution of 99mTc-ahMSCs after IV and IAR administration, via scintigraphic study in an animal model. METHODS: Isolated primary culture of adult human mesenchymal stem cells was labeled with 99mTc-HMPAO for scintigraphic study of in vivo distribution after intravenous and intra-articular (knee) administration in rabbits. RESULTS: IV administration of radiolabeled ahMSCs showed the bulk of radioactivity in the lung parenchyma while IAR images showed activity mainly in the injected cavity and complete absence of uptake in pulmonary bed. CONCLUSIONS: Our study shows that IAR administration overcomes the limitations of IV injection, in particular, those related to cells destruction in the lung parenchyma. After IAR administration, cells remain within the joint cavity, as expected given its size and adhesion properties. ADVANCES IN KNOWLEDGE: Intra-articular administration of adult human mesenchymal stem cells could be a suitable route for therapeutic effect in joint lesions. IMPLICATIONS FOR PATIENT CARE: Local administration of adult human mesenchymal stem cells could improve their therapeutic effects, minimizing side effects in patients.

Imaging and 1-day kinetics of intracoronary stem cell transplantation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Stem cell transplantation is an emerging method of treatment for patients with cardiovascular disease. There are few studies completed or ongoing on stem cell therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Information on stem cell homing and distribution in the myocardium after transplantation might provide important insight into effectiveness of transplantation procedure. AIM: To assess early engraftment, retention and migration of intracoronarily transplanted stem cells in the myocardium of patients with advanced dilated cardiomyopathy of non-ischaemic origin using stem cell labeling with (99m)Tc-exametazime (HMPAO). MATERIALS, METHODS: Thirty-five patients with IDCM and advanced heart failure were included in the study. Autologous hematopoietic (CD34+) stem cells were harvested by peripheral blood apheresis after bone marrow stimulation, labeled with (99m)Tc-HMPAO, tested for viability and injected into coronary vessel supplying areas of myocardium selected by myocardial perfusion scintigraphy as dysfunctional yet viable. Imaging was performed 1h and 18h after transplantation. RESULTS: Myocardial stem cell retention ranged from 0 to 1.44% on early and 0-0.97% on delayed imaging. Significant efflux of stem cells occurred from site of delivery in this time period (p<0.001). Stem cell viability was not affected by labeling. CONCLUSION: Stem cell labeling with (99m)Tc-HMPAO is a feasible method for stem cell tracking after transplantation in patients with IDCM.

99mTc-CXCL8 SPECT to Monitor Disease Activity in Inflammatory Bowel Disease.

UNLABELLED: Inflammatory bowel diseases (IBDs) are defined as chronic relapsing immune-mediated disorders of the gastrointestinal tract. IBD exacerbations are characterized by recruitment of mainly CXCL8 receptor-expressing activated neutrophils into the intestinal wall, leading to severe damage. Considering its chronic relapsing character, accurate and timely diagnosis of an exacerbation is pivotal for early adaptation of the treatment and reduction of the disease burden. However, endoscopic evaluation is invasive and associated with an increased risk of perforation. We previously developed a (99m)Tc-labeled CXCL8 preparation in preclinical models including colitis and clinical studies. METHODS: In this study, we investigate the accuracy of (99m)Tc-CXCL8 SPECT to detect and localize disease activity in a prospective series of patients with IBD. Thirty patients (15 Crohns disease, 15 ulcerative colitis) participated, and 92 segmental pairs of histology and (99m)Tc-CXCL8 scans were studied. Imaging was performed after injection of 400 MBq of (99m)Tc-CXCL8. Planar and SPECT images of the abdomen were acquired at 30 min and 4 h after the injection. RESULTS: The overall sensitivity and specificity on a per-patient basis for the detection of active disease were 95% and 44% for (99m)Tc-CXCL8 scan and 71% and 70% for endoscopy. The degree of (99m)Tc-CXCL8 accumulation correlated to the degree of neutrophilic influx in affected mucosa. Sensitivity and specificity on a per-segment basis, calculated from the 92 segmental pairs, were 82% and 72%, negative predictive value was 81%, and overall positive predictive value was 74%. Specificity could be increased at the expense of sensitivity using different cutoffs. In 74 segmental pairs, overall sensitivity and specificity for endoscopy were 74% and 85%, positive predictive value was 81%, and negative predictive value was 79%. CONCLUSION: (99m)Tc-CXCL8 SPECT provides a novel imaging technique to target neutrophil recruitment to the intestinal wall, especially in moderate to severe exacerbations of IBD. Further validation studies are warranted to potentiate (99m)Tc-CXCL8 SPECT as a biomarker to scale up or step down treatment with immune-modulating drugs in a personalized fashion.

Validation of the leukocyte labeling procedure with a new kit for the preparation of technetium-99m exametazime injection.

The labeling of leukocytes with technetium-99m (Tc)-HMPAO is a frequent procedure in our laboratory, which was first validated before initiation of clinical studies with the commercial kit of Tc-D,L-hexamethylpropylene amine oxime (Tc-D,L-HMPAO), available from 1988. Recently, a new kit of exametazime has been introduced, with a similar composition and clinical indications, but with some technical improvements. Validation of the labeling procedure with this new kit is proposed, including a comparison between both commercial kits. Requirements for validation were achieved successfully and a comparative study showed no statistically significant differences; nevertheless, labeling of leukocytes may be expected routinely with the new kit on account of its longer shelf-life and lower cost.

Arteriovenous fistula stent infection diagnosed with radiolabelled leucocyte scintigraphy.

Infectious complications of haemodialysis in patients with arteriovenous fistula stent are rare. In addition, patients with low-grade infection are more difficult to diagnose. Here, we report the first case of low-grade infection of an arteriovenous fistula stent diagnosed using (99m)Tc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocyte scintigraphy. A 62-year-old man with end-stage renal disease was referred for prolonged fever. We performed (99m)Tc-HMPAO-labelled leucocyte scintigraphy following a work-up according to fever of unknown origin. A focal uptake on the left forearm compatible with the arteriovenous fistula stent insertion site was shown, and the stent was removed. (99m)Tc-HMPAO-labelled leucocyte scintigraphy could be a suitable method for assessing vascular stent infection in low-grade fever.

Incidental bone lesion on 99mTc-exametazime brain perfusion SPECT / Lesión ósea incidental en SPECT cerebral de perfusión con 99mTc-exametazima

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Normal regional distribution of cerebral blood flow in dogs: comparison between (99m) Tc-ethylcysteinate dimer and (99m) Tc- hexamethylpropylene amine oxime single photon emission computed tomography.

Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.

Media Fill Test for validation of autologous leukocytes separation and labelling by (99m)Tc-HmPAO.

OBJECTIVE: Manufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with (99m)Tc-exametazime ((99m)Tc-hexamethylpropyleneamine oxime; (99m)Tc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with (99m)Tc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas (99m)Tc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test. METHODS: The study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth. RESULTS: No evidence of turbidity was observed in all the steps assayed by the Media Fill. CONCLUSIONS: In the separation and labelling of autologous leukocytes with (99m)Tc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process.

Differential lung uptake of 99mTc-hexamethylpropyleneamine oxime and 99mTc-duramycin in the chronic hyperoxia rat model.

UNLABELLED: Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury that occur with acute respiratory distress syndrome, for example. Lung uptake of (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue whereas (99m)Tc-duramycin, a new marker of cell injury, senses cell death via apoptosis or necrosis. Thus, we investigated changes in lung uptake of these agents in rats exposed to hyperoxia for prolonged periods, a common model of acute lung injury. METHODS: Male Sprague-Dawley rats were preexposed to either normoxia (21% O(2)) or hyperoxia (85% O(2)) for up to 21 d. For imaging, the rats were anesthetized and injected intravenously with either (99m)Tc-HMPAO or (99m)Tc-duramycin (both 37-74 MBq), and planar images were acquired using a high-sensitivity modular γ-camera. Subsequently, (99m)Tc-macroagreggated albumin (37 MBq, diameter 10-40 µm) was injected intravenously, imaged, and used to define a lung region of interest. The lung-to-background ratio was used as a measure of lung uptake. RESULTS: Hyperoxia exposure resulted in a 74% increase in (99m)Tc-HMPAO lung uptake, which peaked at 7 d and persisted for the 21 d of exposure. (99m)Tc-duramycin lung uptake was also maximal at 7 d of exposure but decreased to near control levels by 21 d. The sustained elevation of (99m)Tc-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 d. CONCLUSION: These results suggest the potential use of (99m)Tc-HMPAO and (99m)Tc-duramycin as redox and cell-death imaging biomarkers, respectively, for the in vivo identification and assessment of different stages of lung injury.

Added value of 99mTc-HMPAO-labeled leukocyte SPECT/CT in the characterization and management of patients with infectious endocarditis.

UNLABELLED: The clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) can be improved through functional imaging procedures such as radiolabeled leukocytes ((99m)Tc-hexamethylpropyleneamine oxime [HMPAO]-labeled white blood cells [WBC]). METHODS: We assessed the value of (99m)Tc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in a series of 131 consecutive patients with suspected IE. Patients with permanent cardiac devices were excluded. (99m)Tc-HMPAO-WBC scintigraphy results were correlated with transthoracic or transesophageal echocardiography, blood cultures, and the Duke criteria. RESULTS: Scintigraphy was true-positive in 46 of 51 and false-negative in 5 of 51 cases (90% sensitivity, 94% negative predictive value, and 100% specificity and positive predictive value). No false-positive results were found, even in patients with early IE evaluated within the first 2 mo from the surgical procedure. In 24 of 51 patients with IE, we also found extracardiac uptake, indicating septic embolism in 21 of 24. Despite the fact that septic embolism was found in 11 of 18 cases of Duke-definite IE, most of the added value from the (99m)Tc-HMPAO-WBC scan for decision making was seen in patients in whom the Duke criteria yielded possible IE. The scan was particularly valuable in patients with negative or difficult-to-interpret echocardiographic findings because it correctly classified 11 of 88 of these patients as having IE. Furthermore, 3 patients were falsely positive at echocardiography but correctly negative at (99m)Tc-HMPAO-WBC scintigraphy: these patients had marantic vegetations. CONCLUSION: Our results demonstrate the ability of (99m)Tc-HMPAO-WBC scintigraphy to reduce the rate of misdiagnosed cases of IE when combined with standard diagnostic tests in several situations: when clinical suspicion is high but echocardiographic findings are inconclusive; when there is a need for differential diagnosis between septic and sterile vegetations detected at echocardiography; when echocardiographic, laboratory, and clinical data are contradictory; and when valve involvement (especially of a prosthetic valve) needs to be excluded during febrile episodes, sepsis, or postsurgical infections.

Synthesis, radiolabeling and biological evaluation of propylene amine oxime complexes containing nitrotriazoles as hypoxia markers.

Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4-triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 ± 0.2% and 35.0 ± 0.7% at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 ± 1.6% and 4.6 ± 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant anoxic/normoxic differentials. The cellular uptakes were highly dependent on oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At 4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1 and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second nitrotriazole redox center, the hypoxic accumulation of the marker was slightly enhanced.

Adaptación del módulo de 18FDG para la preparación de una disolución inyectable de [18F] fluoruro sódico de conformidad con la Farmacopea Americana (USP 32) y Europea (PhEur 6) / Adaptation of the 18FDG module for the preparation of a sodium fluoride [18F] injection solution in agreement with the United States (USP 32) and European Pharmacopeia (PhEur 6)

Objetivos. Establecer un procedimiento automatizado para la preparación de la disolución inyectable de [18F] NaF utilizando los recursos disponibles en nuestro laboratorio para la preparación de 18FDG, analizando la repercusión del acondicionamiento de la columna de atrapamiento del ion fluoruro sobre las características del producto final. Material y método. Se modificó la secuencia de un módulo de síntesis de 18FDG automatizado de manera que el ion fluoruro procedente del ciclotrón se atrapa en resina de intercambio aniónico y se eluye con cloruro sódico 0,9%. La disolución final se dosifica y autoclava en envase final en equipo automatizado. Dentro del proceso, se estudiaron tres protocolos diferentes de acondicionamiento de columna. Se realizaron los controles de calidad descritos en USP 32 y PhEur 6, añadiendo el control de etanol como disolvente residual y los controles de calidad de la disolución a las 8 h de la preparación. Resultados. La activación de los cartuchos de resina con etanol y agua presenta una atrapamiento del ion fluoruro > 95% y pH en torno a 7, por lo que es el procedimiento de acondicionamiento de elección. La concentración de etanol se mantuvo < 5.000 ppm. Los controles efectuados a las 8 h indicaban que la disolución mantenía las especificaciones de USP 32 y PhEur 6. Conclusiones. Se describe un método automatizado sencillo, económico y reproducible, de preparación de una disolución inyectable de 18F-fluoruro sódico al alcance de cualquier centro con equipamiento convencional para síntesis y control de calidad de 18FDG(AU)

Objective. To establish an automated procedure for the preparation of sodium fluoride 18F injection using the resources available in our laboratory for the preparation of 18FDG and to analyze the repercussion of the conditioning column of the fluoride ion entrapment on the characteristics of the final product. Material and method. The sequence of an 18FDG synthesis module prepared so that it traps the fluoride ion from the cyclotron in ion-exchange resin diluted with 0.9% sodium chloride. The final solution was dosified and sterilized in a final vial in an automatized dispensing module. Three different column conditioning protocols within the process were tested. Quality controls were run according to USP 32 and EurPh 6, adding control of ethanol levels of residual solvent and quality controls of the solution at 8 h post-preparation. Results. Activation of the resin cartridges with ethanol and water was the chosen procedure, with fluoride ion trapping > 95% and pH around 7. Ethanol levels were < 5.000 ppm. Quality controls at 8 h indicated that the solution was in compliance with the USP 32 and EurPh 6 specifications. Conclusion. This is an easy, low-cost, reliable automated method for sodium fluoride preparation in PET facilities with existing equipment for 18FDG synthesis and quality control(AU)