Influence of biomaterials on scintigraphic diagnosis of periprosthetic infections. Ceftizoxime-99m technetium model

Abstract Purpose: To compare the influence of two metallic implants in the diagnosis of periprosthetic infection using 99m technetium-labeled ceftizoxime. Methods: Twenty rats were randomly divided into four groups, which received sterile and contaminated titanium and stainless steel implants. After 3 weeks, scintilographic images were obtained using a gamma chamber. Radioactivity counts were obtained for the region of interest (ROI) on the operated and non-operated paws. Results: Groups A, B, and C showed homogenous distribution of the radiopharmaceutical. Hyper uptake was observed in the operated paw from group D. The ROI target count was higher in the two groups with stainless steel implants. Among the control groups, the count was higher in the stainless steel group. Furthermore, among the contaminated groups, the uptake was higher in the stainless steel group, with a significant difference. The target: non-target ratio was significantly lower in the control and contaminated groups with both titanium and stainless steel, but the comparison between control groups and contaminated groups was only significant in the former. The cpm/g observed after a decay of 48h showed statistically significant differences between groups. Conclusion: Different biomaterials used in implants have an influence on the results of scintigraphy with 99mTc-CFT.

Value of Ga-DOTA-TATE Positron Emission Tomography/Computed Tomography in the Localization of Culprit Tumors Causing Osteomalacia with Negative Tc-HYNIC-TOC Single Photo Emission Computed Tomography / 中国医学科学院学报

Objective To analyze Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) imaging features of tumor-indud osteomalacia (TIO) patients with negative Tc-HYNIC-TOC single photo emission computed tomography (SPECT) findings and to investigate the value of Ga-DOTA-TATE PET/CT in accurate localization of culprit tumors.Methods We retrospectively analyzed Ga-DOTA-TATE PET/CT imaging features including location,size,density,the maximum and mean standardized uptake value in 37 TIO patients with negative Tc-HYNIC-TOC SPECT findings.Results Totally 37 solitary TIO tumors,including 35 phosphaturic mesenchymal tumors and 2 spindle cell tumors confirmed by pathological examinations,were detected via Ga-DOTA-TATE PET/CT scans in the included 37 cases. These 37 TIO tumors showed obviously increased activities,with an maximum standardized uptake value of 7.2±4.3 and mean standardized uptake value of 4.3±2.4. The average maximum diameter was (1.9±0.7) cm. The majority of the tumors occurred in the lower extremities (19/37),followed by the trunk (11/37),maxillary/mandibular bone (5/37),and upper extremities (2/37). In addition,24 bone lesions were located in long bones of lower extremities (13/24),most of which demonstrated eccentric growth (8/13). Osteolytic changes (14/24) were observed mainly in the lesions via the corresponding CT imaging;meanwhile,sclerotic changes presented in nine cases. Of the 13 soft-tissue lesions,the majority (10/13) showed well-circumscribed isodense or hypodense nodules on the CT images,with spot calcification in one lesion located in the pleura.Conclusions Ga-DOTA-TATE PET/CT scans can detect the TIO culprit tumors miss-diagnosed by Tc-HYNIC-TOC SPECT. Somatostatin-receptors highly expressed lesions with focal osteolytic or osteosclerotic change in bone and isodense or hypodense nodules in soft tissue will favor the diagnosis of TIO tumors.

Formulation of lyophilized single vial kit of N-N-Ethylene-L-Dicysteine 99m [EC] for labeling with Tc. II: Radiochemical and clinical evaluation 99mr as a renal tubular agent in comparison with Tc-MAG[3]

A Technetium[99m]Tc labeled lyophilized single component kit of N-N-ethylene-I-dicysteine [EC] is developed to replace multiple step kit developed by others. The aim of study is to formulate a radionuclide that is easy to prepare, has rapid plasma clearance, produce high quality images and is an affective alternative to radioiodine labeled orthoiodohippurate, which has been remained the physiological 'gold standard' since long time. To achieve this goal, the systematically varied key parameters such as pH, the use of reducing agents, stabilizers and additives are optimized to obtain maximum radiochemical purity and optimum bio distribution in non human and human primates. Various pH levels of EC showed equally good results in animal experiments but only pH 10 was suitable for human use. Dynamic and renal Scintigraphic studies are carried out with[99m]Tc-EC at pH 8 in 12 volunteers and at pH 10 in 18 volunteers and compared with[99m]Tc-MAG[3], Background ratios, renograms, relative renal function and semi quantitative parameters are available in all studies. The background ratios [mean +/- SD] at 30[th] minute are 0229+/-0.024 and 0.236+/-0.018 for[99m]Tc-EC at pH 10 and[99m]c-MAG[3] respectively. The mean +/- standard error of mean [SEM] values of T[M]X and time to half activity [T[12]] for[99m]Tc-EC [pHIO] are 3.7+/-0.6 and 7.3+/-1.0 respectively while for [99m]Tc-MAG[3], they are 4.0+/-0.8 and 7.9+/-1.4 with p values 0.001 and 0.049 respectively. The values of relative renal function [RRF] for[99m]Tc-EC and[99m]Tc-MAG[3] are 50.8+/-3.11 and 51.2+/-3.4 respectively with p value of 0.822. The residual activity at 25[th] minute [A[25] / A[MAX]] and renal uptake are 0. 209+/-12.67+/-2.80 for[99m]Tc-EC and 0.218+/-0.035 and 1053+/-2.98 for[99m]Tc-MAG[3] [p=0.031 an 0.0003] respectively. The correlation coefficient [R] for T[max], T1/2, A[2]5/A[Max] and renal uptake are 0.96, 0.69, 0.93 and 0.85 respectively

Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.

The Benefits of Prone SPECT Myocardial Perfusion Imaging in Reducing Both Artifact Defects and Patient Radiation Exposure / Benefício da Aquisição de Imagem na Posição Prona em Perfusão Miocárdica com SPECT para Redução de Artefatos e Exposição do Paciente à Radiação

AbstractBackground:Prone imaging has been demonstrated to minimize diaphragmatic and breast tissue attenuation.Objectives:To determine the role of prone imaging on the reduction of unnecessary rest perfusion studies and coronary angiographies performed, thus decreasing investigation time and radiation exposure.Methods:We examined 139 patients, 120 with an inferior wall and 19 with an anterior wall perfusion defect that might represented attenuation artifact. Post-stress images were acquired in both the supine and prone position. Coronary angiography was used as the “gold standard” for evaluating coronary artery patency. The study was terminated and rest imaging was obviated in the presence of complete improvement of the defect in the prone position. Quantitative interpretation was performed. Results were compared with clinical data and coronary angiographic findings.Results:Prone acquisition correctly revealed defect improvement in 89 patients (89/120) with inferior wall and 12 patients (12/19) with anterior wall attenuation artifact. Quantitative analysis demonstrated statistically significant difference in the mean summed stress scores (SSS) of supine and mean SSS of prone studies in patients with disappearing inferior wall defect in the prone position and patent right coronary artery (true negative results). The mean difference between SSS in supine and in prone position was higher with disappearing than with remaining defects.Conclusion:Technetium-99m (Tc-99m) tetrofosmin myocardial perfusion imaging with the patient in the prone position overcomes soft tissue attenuation; moreover it provides an inexpensive, accurate approach to limit the number of unnecessary rest perfusion studies and coronary angiographies performed.

ResumoFundamento:Já foi demonstrado que a imagem na posição prona minimiza a atenuação dos tecidos diafragmáticos e da mama.Objetivos:Determinar o papel da imagem na posição prona na redução de estudos de perfusão em repouso e angiografias coronárias realizadas de forma desnecessária, assim diminuindo o tempo de investigação e exposição à radiação.Métodos:Foram examinados 139 pacientes, 120 com um defeito de perfusão da parede inferior e 19 com defeito de perfusão da parede anterior que pudessem representar um artefato de atenuação. Imagens pós-estresse foram adquiridas nas posições supina e prona. A angiografia coronária foi usada como o “padrão ouro” para avaliar a patência da artéria coronária. O estudo foi encerrado e a imagem em repouso não foi necessária na presença de melhoria completa do defeito na posição prona. Uma interpretação quantitativa foi realizada. Os resultados foram comparados com os dados clínicos e achados angiográficos.Resultados:A aquisição de imagem na posição prona revelou corretamente a melhoria do defeito em 89 pacientes (89/120) com artefato de atenuação na parede inferior e 12 pacientes (19/12) na parede anterior. A análise quantitativa demonstrou diferença estatisticamente significante nas somas dos escores de estresse (SSS) médios nos estudos da posição supina e SSS médios dos estudos na posição prona em pacientes com desaparecimento do defeito da parede inferior na posição prona e artéria coronária patente (resultados negativos verdadeiros). A diferença média dos SSS nas posições supina e prona foi maior com os defeitos desaparecidos do que com os que permaneceram.Conclusão:A cintilografia de perfusão miocárdica com Tecnécio-99m (Tc-99m) tetrofosmin com o paciente na posição prona supera a atenuação de tecidos moles; Além disso, oferece uma abordagem precisa e de baixo custo para limitar o número de estudos de perfusão em repouso e realização de angiografias coronárias desnecessárias.

Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14) as an agent for pancreas tumor detection in mice

Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using99mTc-HYNIC-βAla-Bombesin(7-14)as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that99mTc-HYNIC-βAla-Bombesin(7-14)uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that99mTc-HYNIC-βAla-Bombesin(7-14)may be useful for the detection of pancreatic adenocarcinoma.

Scintigraphic imaging with technetium-99M-labelled ceftizoxime is a reliable technique for the diagnosis of deep sternal wound infection in rats

PURPOSE:To evaluate whether scintigraphy with technetium-99m-labeled ceftizoxime (99mTc-CFT) can differentiate mediastinitis from aseptic inflammation associated with sternotomy.METHODS:Twenty female Wistar rats were randomly distributed into four groups: S (control) -partial upper median sternotomy with no treatment; SW (control) - sternotomy and treatment of sternal wounds with bone wax; SB - sternotomy and infection with Staphylococcus aureus; SWB - sternotomy with bone wax treatment and bacterial infection. Scintigraphy with 99mTc-CFT was performed eight days after surgery and images were collected 210 and 360 min after infusion of the radiopharmaceutical.RESULTS: No animals exhibited clinical signs of wound infection at the end of the experiment, although histological data verified acute inflammatory response in those experimentally infected with bacteria. Scintigraphic images revealed that tropism of 99mTc-CFT to infected sternums was greater than to their non-infected counterparts. Mean counts of radioactivity in bacteria-infected sternal regions (SB and SWB) were significantly higher (p = 0.0007) than those of the respective controls (S and SW).CONCLUSION:Scintigraphy with technetium-99m-labeled ceftizoxime is a method that can potentially detect infection post sternotomy and differentiate from aseptic inflammation in animals experimentally inoculated with S. aureus.

comparison between estimates of glomerular filtration rate using technetium-99m-diethylene-triamine-pentaacetic acid clearance and modification of diet in renal disease equation

Background: More than half of cancer patients have unrecognized renal insufficiency, which is a reduced glomerular filtration rate [GFR] and is a disease complication factor

Aims and Objectives: The objective of the present study is to compare the accuracy of GFR with two methods, i.e., GFR by Gates' method [gamma camera uptake method with technetium-99m-diethylene-triamine-pentaacetic acid [Tc-99m-DTPA] and GFR by modification of diet in renal disease [MDRD] equation in cancer patients

Materials and Methods: A total of 50 cancer patients with abnormal serum creatinine were included in the study. 50 age matched cancer patients with normal creatinine, blood urea nitrogen [BUN] and serum albumin were taken as controls. History of patients including site of cancer, chemotherapy regime and dose of chemotherapy was recorded. Serum creatinine was estimated by auto analyzer using Jaffe's method. Glomerular filtration rate [GFR] was calculated using camera based modified gates method with [99mTc-DPTA] and MDRD equation

Results: Mean age of patients was 50 year. Level of serum creatinine and BUN were significantly increased [P < 0.001] in patients when compared to controls. Level of serum albumin was non-significantly [P > 0.05] decreased in cancer patients and body surface area also increased, but differences were non-significant [P > 0.05] in cancer patients when compared to controls. Mean GFR was estimated by camera based modified gates method which increased in cancer patients as compared to GFR by MDRD equation but differences were not significant [P > 0.05]. Cost, time duration and time for reagent preparation was very high using Renogram [Gate's method] as compared to the cost and other factors involved in estimation of GFR by MDRD equation

Conclusions: It is concluded that the MDRD equation is more suitable, economical and time saving for the estimation of GFR as compared to Renogram using Tc-99m-DPTA. However future prospective studies are required to the estimation of GFR in those tumors, which may cause kidney damage such as cisplatin or carboplatin, methotrexate

Radioactive probe-guided parathyroidectomy for secondary hyperparathyroidism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The value of gamma probes in the surgical treatment of secondary hyperparathyroidism (sHPT) was determined. The aim of this study was to enhance the rate of successful total parathyroidectomy in patients with sHPT using intraoperative gamma probe investigations.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 48 sHPT patients between May 2007 and September 2011. Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high-frequency ultrasonography were used for parathyroid localization. Thirty-five patients (group I) underwent conventional neck exploration and open parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided total parathyroidectomy and parathyroid transplantation. The two groups were compared in terms of the number of parathyroid resections, operative time, and postoperative changes in the blood levels of parathyroid hormone (PTH), calcium, and phosphate.</p><p><b>RESULTS</b>The clinical manifestations, PTH and calcium levels, age distribution, and clinical characteristics did not differ between the two groups. The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the diagnosis of hyperparathyroidism did not differ from that of ultrasonography (81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for localizing hyperfunctioning parathyroids was significantly lower than that of ultrasonography (76.86%). The operation time was significantly longer in group I ((120 ± 25) minutes) than in group II ((90 ± 30) minutes). The accuracy of parathyroid identification was significantly higher in group II (92.59%) than in group I (80.39%). On average, significantly fewer parathyroid specimens were obtained in group I (2.5 ± 0.5) than in group II (3.5 ± 0.5). Compared with group I, group II showed a significant increase (15.4%) in the number of parathyroid resections. The PTH, calcium, and phosphate levels significantly decreased postoperatively in all patients.</p><p><b>CONCLUSIONS</b>Intraoperative gamma probe examination confirmed that the excised specimen was parathyroid tissue and improved the accuracy of parathyroid resection. The parathyroidectomy rate was increased by 15.4% due to the use of these probes. However, the probes did not detect all ectopic parathyroids, and further research is required to clarify the underlying reasons.</p>

The ileum as a determinant organ of the functional liver cell mass in rats

PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6) and sham group rats (n = 6). After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate (0.66MBq) was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytate percentage of radioactivity/gram of tissue and histopathology. Student 's t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p<0.05). GammaGT, ALT and AST were increased in ileum resection rats compared to sham (p<0.05). The he patocytes count was significantly lower in ileum resection group than in sham (p<0.05). Liver: body mass ratio was lower in experimental animals than in sham group (p<0.05). CONCLUSION: These data support that the ileum has important role in liver function and liver mass regulation, and they have potential clinical implications regarding the pathogenesis of liver injury following lower bowel resection.

99mTc-thymine scintigraphy may be a promising method in the diagnosis of breast cancer

OBJECTIVE: Mammography has been established as the gold standard for the detection of breast cancer, and imaging techniques such as ultrasonography, magnetic resonance imaging, scintigraphy and positron emission tomography may be useful to improve its sensitivity and specificity. The objective of this study with breast scintigraphy was to evaluate the uptake of 99mTc-thymine in mammary lesions. METHODS: A total of 45 patients were included in this study. Thirty-three patients (73%) were subjected to surgery or percutaneous biopsy, providing histopathological data. The other 12 patients who remained under surveillance received clinical examinations and biannual mammography with a normal follow-up of at least three years, the data from which were used for comparison with the scintimammography results. RESULTS: The majority of patients (64.4%) had clinically impalpable lesions with a mammogram diagnosis of microcalcifications, impalpable nodules, or focal asymmetry. Of the studied lesions, 87% were smaller or equal to 20 mm in diameter, and 22% had malignant histopathological findings. Scintigraphy with 99mTc-thymine had a sensitivity of 70%, a specificity of 85.7%, positive and negative predictive values of 58.3% and 90.9%, respectively, and an accuracy of 82.2%. CONCLUSIONS: The results of this study are consistent with those previously reported by other authors. The good specificity and high negative predictive value of this technique and the absence of uptake in the heart indicate that it may be a promising complementary method in clinical practice and that it may contribute to reducing unnecessary benign biopsies.

Bone Positron Emission Tomography with or without CT Is More Accurate than Bone Scan for Detection of Bone Metastasis

OBJECTIVE: Na18F bone positron emission tomography (bone PET) is a new imaging modality which is useful for the evaluation of bone diseases. Here, we compared the diagnostic accuracies between bone PET and bone scan for the detection of bone metastasis (BM). MATERIALS AND METHODS: Sixteen cancer patients (M:F = 10:6, mean age = 60 +/- 12 years) who underwent both bone PET and bone scan were analyzed. Bone PET was conducted 30 minutes after the injection of 370 MBq Na18F, and a bone scan was performed 3 hours after the injection of 1295 MBq 99mTc-hydroxymethylene diphosphonate. RESULTS: In the patient-based analysis (8 patients with BM and 8 without BM), the sensitivities of bone PET (100% = 8/8) and bone scan (87.5% = 7/8) were not significantly different (p > 0.05), whereas the specificity of bone PET (87.5% = 7/8) was significantly greater than that of the bone scan (25% = 2/8) (p < 0.05). In the lesion-based analysis (43 lesions in 14 patients; 31 malignant and 12 benign), the sensitivity of bone PET (100% = 31/31) was significantly greater than that of bone scan (38.7% = 12/31) (p < 0.01), and the specificity of bone PET (75.0% = 9/12) was also significantly higher than that of bone scan (8.3% = 1/12) (p < 0.05). The receiver operating characteristic curve analysis showed that bone PET was significantly more accurate than the bone scan in the patient (p = 0.0306) and lesion (p = 0.0001) based analyses. CONCLUSION: Na18F bone PET is more accurate than bone scan for BM evaluation.

(99m)Tc radiolabeling of a novel polypeptide molecular probe for lung cancer and its biodistribution in animals / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop a method for (99m)Tc radiolabeling of a small molecular peptide targeting lung carcinoma and observe the biokinetics and biodistribution of the labeled peptide in normal mice and rabbits.</p><p><b>METHODS</b>MAG3-peptide (cNGQGEQc) was labeled with (99m)Tc and the labeling rate was determined with paper chromatography. In vitro stability test, cysteine challenge test and serum incubation test were performed for radiochemical evaluation of the labeled peptide. Blood (99m)Tc-peptide clearance in rabbits was evaluated by determining blood radioactive concentrations at different time points after injection of 37 MBq (99m)Tc-peptide, and its dynamic distribution was investigated by SPECT imaging. The percent injected dose per gram of tissue was calculated for each organ of mice injected intravenously with 7.4 MBq (99m)Tc-peptide based on gamma counter readings.</p><p><b>RESULTS</b>The labeling rate of (99m)Tc-peptide exceeded 90%, and the radiochemical purity was 91% after placing for 12 h at room temperature and 85% after incubation at 37 degrees celsius; with human serum. The cysteine replacement rate was less than 7%, and the binding rate of (99m)Tc-peptide with serum proteins was below 5%. SPECT imaging showed that the labeled peptide could be quickly cleared from the blood in normal animals primarily through the kidneys, and the radioactivity in other tissues and organs remained low.</p><p><b>CONCLUSION</b>(99m)Tc-peptide can be easily prepared with a high labeling yield. With good stability both in vitro and in vivo, (99m)Tc-peptide can be quickly cleared from the blood and excreted though the kidney with ideal biodistribution and biokinetics in vivo.</p>

An Incidentally Found Inflamed Uterine Myoma Causing Low Abdominal Pain, Using Tc-99m-Tektrotyd Single Photon Emission Computed Tomography-CT Hybrid Imaging

We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

A preliminary study of imaging paclitaxel-induced tumor apoptosis with (99)Tc(m)-His10-Annexin V / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.</p><p><b>METHODS</b>(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.</p><p><b>RESULTS</b>(99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01).</p><p><b>CONCLUSION</b>This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.</p>

Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.

Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of Scans Without Evidence of Dopaminergic Deficit (SWEDDs) / Neuroimagem do transportador de dopamina em casos de parkinsonismo clinicamente indefinidos e a importância dos SWEDDs (exames sem evidência de déficit dopaminérgico)

The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We described four representative patients with clinically unclear parkinsonian syndromes who underwent [99mTc]-TRODAT-1 SPECT and reviewed the clinical implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.

O diagnóstico clínico da doença de Parkinson (DP) pode estar sujeito a erros especialmente nas fases iniciais da doença. Recentemente, técnicas de imagem in vivo que avaliam o transportador de dopamina pré-sináptico (DAT) surgiram como uma ferramenta empregada no diagnóstico da DP, melhorando sua acurácia. OBJETIVO: Foi demonstrar a utilização clínica de um traçador de tomografia computadorizada por emissão de fóton único (SPECT) e destacar importantes aspectos dos casos de SWEDDs (exames sem evidência de déficit dopaminérgico) neste contexto. CASOS: Descrevemos quatro pacientes representativos de síndromes parkinsonianas clinicamente incertas submetidos a [99mTc]-TRODAT-1 SPECT e revisamos suas implicações. CONCLUSÃO: O DAT-SPECT é uma técnica importante e eficiente para o diagnóstico diferencial das síndromes parkinsonianas. Além disso, os casos de SWEDDs apresentam peculiaridades clínicas e paraclínicas que podem retrospectivamente identificá-los como tremor essencial ou tremor distônico. As conclusões têm alcance limitado pela falta de dados histopatológicos.

Evaluation of Cardiovascular Disease in Patients with Diabetes Mellitus Using Myocardial Perfusion SPECT / 임상당뇨병

The number of patients with diabetes mellitus increases every year. Compared with the nondiabetic population, diabetic patients have an increased risk of developing cardiovascular disease and an increased risk for death from myocardial infarction or congestive heart failure. In diabetic patients, compared with people without diabetes, coronary artery disease is often silent, more advanced at diagnosis, and associated with an unfavorable prognosis. To maximize the effect of appropriate treatment, it is important to stratify patients according to their risk of future clinical events as early as possible. Commonly used noninvasive tests in coronary artery disease include exercise ECG, stress echocardiography, coronary CT and MRI, and stress myocardial perfusion SPECT. The generally used radioisotopes for myocardial perfusion SPECT are 201Tl and technetium-based agents such as 99mTc-MIBI and 99mTc-tetrofosmin. Stress myocardial perfusion SPECT provides information on perfusion and function including wall motion, ejection fraction, and myocardial viability. Also, the hemodynamic significance of coronary artery stenosis can be assessed. Stress myocardial perfusion SPECT provides quantifiable data and identifies patients with diabetes who are at low and high risk for future adverse cardiovascular events. These risk stratification data are useful in planning appropriate treatment strategies for patients with diabetes.

effect of prednisolone on the sensitivity of Technetium 99m-methylene diphosphonate [[99m] Tc-MDP] scintigraphy to detect simulated closed fracture in the rat tibia

The purpose of the present study was to evaluate the effect of prednisolone on the sensitivity of bone scanning to detect the simulated closed fracture in the rat tibia. A total number of forty eight adult, male NMRI rats randomly assigned into two parts, one part for 4 and other for 8 weeks experiments. Each part has been divided into four groups, one group not receiving prednisolone [control group] and the other groups receiving 5, 10 and 20 mg/kg prednisolone respectively. After four and eight weeks of experiments a simulated closed fracture was created in the tibia approximately 1 cm near knee joint. .The scintigraphy imaging has been performed on second and fifth day after tibial bone fracture and the ratio of the activity of tibia bone fracture to the contra lateral healthy side was calculated [R factor]. All scintigraphy images showed the rat tibia bone fracture. Statistically significant difference in the R factors have been observed, when scintigraphy images were performed in fifth day after injury. Bone radionuclide scanning by [99m]Tc-MDP is very sensitive for detection of occult fracture. In order to enhance bone scan sensitivity, it may be reasonable to postpone [99m]Tc-MDP scintigraphy imaging at least 2 to 3 days after suspected trauma in patients receiving glucocorticoid medication