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.

Valor diagnóstico de la gammagrafía de perfusión miocárdica con 99mTc-Tetrofosmina en mujeres previamente revascularizadas / Diagnostic value of myocardial perfusion imaging with 99mTc-tetrofosmin in a population of women previously revascularized

Fundamento y objetivo: Se trata de un estudio transversal donde se han determinado los valores de sensibilidad y especificidad del estudio de perfusión miocárdica con 99mTc-Tetrofosmina en protocolo de un día tras estímulo farmacológico con dipiridamol, en una población de mujeres previamente revascularizadas, así como la relación con los territorios vasculares coronarios, tomando como referencia la coronariografía. Pacientes: Se han estudiado con carácter retrospectivo 53 historias clínicas de mujeres sometidas a una prueba de perfusión miocárdica y a una coronariografía de control. Resultados: Los valores de sensibilidad y especificidad para la población fueron de 64,29 por ciento y 75,0 por ciento respectivamente. Por territorio arterial coronario, los valores de sensibilidad y especificidad para la arteria DA fueron de 68,75 por ciento y 75,0 por ciento respectivamente, para la Cx de 37,93 por ciento y 88,89 por ciento, y para la CD de 46,43 por ciento y 60,71 por ciento. Conclusiones: En las mujeres que han sido previamente revascularizadas, la gammagrafía de perfusión miocárdica con 99mTc-Tetrofosmina y dipiridamol en protocolo de un día parece ser una prueba idónea para realizar el seguimiento de pacientes.

Background: This is a cross-sectional study to identify the values of sensitivity and specificity of myocardial perfusion imaging with 99mTc-tetrofosmin one-day protocol after pharmacological stimulation with dipyridamole in a population of women previously revascularized and the relationship of findings to coronary vascular territories, with coronary angiography as a gold standard. Patients We studied retrospectively 53 medical records of women undergoing myocardial perfusion test and control coronary angiography. Results: The sensitivity and specificity for the population were 64.29 percent and 75.0 percent respectively. For coronary artery territory, the values of sensitivity and specificity for the LAD were 68.75 percent and 75.0 percent respectively, for Cx of 37.93 percent and 88.89 percent, and for the RCA 46.43 percent and 60.71 percent. Conclusions: In women who have been previously revascularized, myocardial perfusion scintigraphy with 99mTc-tetrofosmin and dipyridamole in one-day protocol seems to be a suitable test to monitor patients.

Clinical Significance of Reverse Redistribution Phenomenon on Delayed Tc-99m Tetrofosmin Myocardial Perfusion Imaging in Patients with Acute Myocardial Infarction / 핵의학분자영상

PURPOSE: This study was performed to investigate the clinical significance of reverse redistribution (RR) phenomenon detected on delayed Tc-99m tetrofosmin myocardial single photon emission computed tomography (SPECT) in patients with acute myocardial infarction after revascularization. MATERIALS AND METHODS: A Tc-99m tetrofrosmin myocardial SPECT was performed in 67 consecutive patients after revascularization for acute myocardial infarction. Myocardial SPECT imaging was performed for early imaging at 40 min and for delayed imaging at 180 min after reinjection at myocardial stress. Regional myocardial uptakes were scored by 4-point scoring in the left ventricular wall divided into 17 segments. Reverse redistribution was defined as an increase of more than 2 point in the activity score on the delayed image. Follow-up myocardial SPECT and coronary angiography (CAG) were performed 9 months later. RESULTS: On myocardial SPECT performed following revascularization, RR was observed in 100 of all 319 segments (31%) and in 43 patients (64%). The abnormalities of perfusion and regional wall motion were more severe in the patients with RR compared to those without RR (p<0.05). On follow-up myocardial SPECT, the myocardial perfusion, regional wall motion, and myocardial thickness were significantly improved in the patients with RR (p<0.05) however, these changes were not significant in those without RR. There was no significant difference between the patients with RR and those without RR in the occurrence of restenosis on CAG. CONCLUSIONS: In patients with acute myocardial infarction, the regions showing the RR phenomenon on delayed Tc-99m tetrofosmin SPECT may reflect viable myocardium and indicate recovery of salvaged myocardium.

The Clinical Usefulness of 99mTc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement / 华中科技大学学报（医学）（英德文版）

Summary: In order to investigate the clinical significance of 99mTc-Tetrofosmin (TF) seintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmonary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target (T/N) ratio between the lung cancer group and the benign lesion group (P<0.001). Moreover, in the lung cancer group, T/N ratio in tomographies was significantly higher than that in planar images (P<0.01). The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas (P<0.05 and P<0.01 respectively), so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinai lymphoid node metastasis (P<0.05). It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas (P<0.05), and 2 h washout rate (WR) of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas (P<0.05). In conclusion, 99mTc-TF scintigraphy showed a favorable diagnostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

The Clinical Efficacy of Lung to Heart Ratio in 1 Hour Delayed Tc-99m Tetrofosmin Gated Myocardial SPECT after Adenosine Stress: Comparison with Coronary Angiography / 핵의학분자영상

PURPOSE: It is well known that lung to heart ratio (LHR) is one of the high risk findings in Tl-201 myocardial perfusion SPECT. We evaluated the clinical efficacy of LHR to identify severe coronary artery disease in adenosine stress Tc-99m tetrofosmin gated myocardial perfusion SPECT (gSPECT). MATERIALS AND METHODS: The study population was 157 patients who underwent both adenosine stress Tc-99m gSPECT and coronary angiography (CAG) within one month. According to the results of CAG and gSPECT LHR and the incidence of increased LHR were compared. RESULTS: Among 53 patients with normal coronary arteries increased LHR was found in 2 patients (3.8%) and 0 in 44 patients (0%) with one vessel disease, 2 in 27 with two vessel disease (7.4%) and 8 in 33 with triple vessel disease (24.2%). Significant differences were found in LHR between subgroups of summed stress score, summed rest score and LV ejection fraction (LVEF). There were weak negative correlation between LHR and LVEF and weak positive correlation between LHR and SSS and SRS. CONCLUSION: Increased LHR had higher incidence in patients with triple vessel disease, severe LV dysfunction and/or extensive perfusion defect than those of normal group. Although its sensitivity might be low to identify severe coronary artery disease, LHR could be helpful in abnormal myocardial perfusion SPECT to stratify risk and prognosis.

Respiratory Motion Detection and Correction in ECG-Gated SPECT: a New Approach

OBJECTIVE: Gated myocardial perfusion single-photon emission computed tomography (GSPECT) has been established as an accurate and reproducible diagnostic and prognostic technique for the assessment of myocardial perfusion and function. Respiratory motion is among the major factors that may affect the quality of myocardial perfusion imaging (MPI) and consequently the accuracy of the examination. In this study, we have proposed a new approach for the tracking of respiratory motion and the correction of unwanted respiratory motion by the use of respiratory-cardiac gated-SPECT (RC-GSPECT). In addition, we have evaluated the use of RC-GSPECT for quantitative and visual assessment of myocardial perfusion and function. MATERIALS AND METHODS: Twenty-six patients with known or suspected coronary artery disease (CAD)-underwent two-day stress and rest (99m)Tc-Tetrofosmin myocardial scintigraphy using both conventional GSPECT and RC-GSPECT methods. The respiratory signals were induced by use of a CT real-time position management (RPM) respiratory gating interface. A PIO-D144 card, which is transistor-transistor logic (TTL) compatible, was used as the input interface for simultaneous detection of both ECG and respiration signals. RESULTS: A total of 26 patients with known or suspected CAD were examined in this study. Stress and rest myocardial respiratory motion in the vertical direction was 8.8-16.6 mm (mean, 12.4 +/- 2.9 mm) and 7.8-11.8 mm (mean, 9.5 +/- 1.6 mm), respectively. The percentages of tracer intensity in the inferior, inferoseptal and septal walls as well as the inferior to lateral (I/L) uptake ratio was significantly higher with the use of RC-GSPECT as compared to the use of GSPECT (p < 0.01). In a left ventricular ejection fraction (LVEF) correlation analysis between the use of rest GSPECT and RC-GSPECT with echocardiography, better correlation was noted between RC-GSPECT and echocardiography as compared with the use of GSPECT (y = 0.9654x + 1.6514; r = 0.93, p < 0.001 versus y = 0.8046x + 5.1704; r = 0.89, p < 0.001). Nineteen (19/26) patients (73.1%) showed abnormal myocardial perfusion scans with reversible regional myocardial defects; of the 19 patients, 14 (14/26) patients underwent coronary angiography. CONCLUSION: Respiratory induced motion can be successfully corrected simultaneously with the use of ECG-gated SPECT in MPI studies using this proposed technique. Moreover, the use of ECG-gated SPECT improved image quality, especially in the inferior and septal regions that are mostly affected by diaphragmatic attenuation. However, the effect of respiratory correction depends mainly on the patient respiratory pattern and may be clinically relevant in certain cases.

Detection of Occult Thymoma Using Tc-99m tetrofosmin Scintigraphy / 핵의학분자영상

Tetrofosmin is a ligand that forms a lipophilic, cationic complex with Tc-99m.1) Tc-99m tetrofosmin was developed as a myocardial perfusion imaging agent and also used to depict tumors.1-3) Mediastinal tumors is also detected by Tc-99m tetrofosmin.2-5) We report a case of extracardiac mediastinal activity detected by Tc-99m tetrofosmin scintigraphy, which revealed thymoma.

Analysis of Myocardial Function Using Gated Myocardial SPECT : Comparison of QGS, 4D-MSPECT Software and Echocardiography / 핵의학분자영상

PURPOSE: Gated myocardial perfusion SPECT provides not only myocardial perfusion status but also various functional parameters of left ventricle. We compared left ventricular ejection fraction, end-diastolic volume, LV mass by cardiac SPECT using Quantitative Gated SPECT (QGS), 4D-MSPECT software and standard 2D-echocardiography. MATERIALS AND METHODS: One hundred fourteen patients (male 51, female 63; 29-85 years old, mean 61.3+/-13.3 years old) with normal perfusion status on Tc-99m tetrofosmin gated myocardial perfusion SPECT were analyzed retrospectively. Ejection fraction (LVEF), End-diastolic volume (LVED), LV mass (LVM) were calculated using QGS, 4D-MSPECT, and LVEF, LVM using 2D-echocardiography. Statistical analysis including Bland-Altman plot was performed using MedCalc(R) (MedCalc software, Mariakerke, Belgium). RESULTS: The correlation of LVEF between methods was good: 0.95/0.96 (stress/rest) between QGS and 4D-MSPECT, 0.79 between QGS and echocardiography, 0.79 between 4D-MSPECT and echocardiography (p<0.001). Using Bland-Altman plot, the 95% confidence interval of agreement between QGS and 4D-MSPECT ranged from -12.7% to 7.3% / from -12.2% to 6.5% (stress/rest). The agreement between QGS and echocardiography, 4D-MSPECT and echocardiography ranged from -17.4% to 24.0%, and -14.8% to 27.0% respectively. The correlation of LVM between methods was also good: 0.95 between QGS and 4D-MSPECT, 0.76 between QGS and echocardiography, 0.73 between 4D-MSPECT and echocardiography (p<0.001). The 95% confidence interval of agreement between QGS and 4D-MSPECT ranged from -33.8 g to 14.1 g (stress/rest). The 95% confidence interval of agreement between QGS and echocardiography, 4D-MSPECT and echocardiography ranged from -148.7 g to 21.8. g, and -142.8 g to 35.5 g, respectively. CONCLUSION: There was a good correlation for LVEF, LVED, LVM among methods (QGS, 4D-MSPECT, echocardiography), but the variance between methods was big. Therefore, the functional parameters by each method cannot be used interchangeably.

Discordant results in Tc-99m tetrofosmin and Tc-99m sestamibi parathyroid scintigraphies

Parathyroid scintigraphies have been used to detect pathological parathyroid glands either before as well as after the parathyroid resection surgery in patients with hyperparathyroidism. One of the most utilized techniques to perform the studies is the double-phase images with Tc-99m sestamibi, which has been shown to be very accurate in the localization of enlarged parathyroid glands. Similar to Tc-99m sestamibi, Tc-99m tetrofosmin is a radiopharmaceutical initially developed to perform myocardial perfusion study that has been used to perform parathyroid scintigraphies. Although most of the papers suggest that the overall sensitivities of both radiopharmaceuticals are similar, there are some papers questioning the accuracy of Tc-99m tetrofosmin to detect abnormal parathyroid glands. In the present article, we report a case with discordant results by both methods.

A cintilografia das paratireóides tem sido utilizada para detectar glândulas paratireóides patológicas tanto antes quanto após (em caso de insucesso) a cirurgia de ressecção em pacientes com hiperparatireoidismo. Uma das técnicas mais utilizadas para realizar este exame é a de duas fases utilizando como radiofármaco o sestamibi-99mTc, a qual tem se mostrado acurada na localização de glândulas paratireóides aumentadas. Similarmente ao sestamibi-99mTc, o tetrofosmin-99mTc é um radiofármaco que foi inicialmente desenvolvido para a realização de cintilografia de perfusão do miocárdio e que tem sido utilizado para a realização de cintilografia das paratireóides. Apesar de muitos artigos sugerirem que as sensibilidades dos dois radiofármacos são idênticas, alguns poucos trabalhos questionam a acurácia do tetrofosmin-99mTc para a localização de glândulas paratireóides anômalas. No presente artigo, relatamos um caso em que foi observado resultado discordante pelos dois métodos.

Effectiveness of 99mTc-tetrofosmin for assessment of heart functions in micropigs

This study examined the suitability of a nuclear imagingtechnique using 99mTc-tetrofosmin as an agent to assess theheart functions of healthy micropigs. The mean age of thepigs was 360 days (male), and the mean body weight was35.3kg ranging from 34.5-36kg. There were no significantperfusion defects in any of the reconstructed images.Gated single-photon emission computed tomographyimaging can be used to calculate the ventricular volumeand ejection fraction (EF). In this case, an EF of 79% wascalculated from the ventricular volume of the end-systolicimage (10 ml) subtracted from that of the end-diastolicvolume (49 ml). A perfusion defect (particularly the apex,lateral wall) is unlikely because of the presence of apreserved wall motion in a segment with a defect. It isconcluded that quantitative cardiac scintigraphy, using99mTc-tetrofosmin is an adequate technique for estimatingthe heart functions of healthy micropigs.

In Vitro Study of Tumor Seeking Radiopharmaceutical Uptake by Human Breast Cancer Cell Line MCF-7 after Paclitaxel Treatment / 핵의학분자영상

PURPOSE: This study was designed to investigate the cellular uptake of various tumor imaging radiopharmaceuticals in human breast cancer cells before and after paclitaxel exposure considering viable cell number. MATERIALS AND METHODS: F-18-fluorodeoxyglucose, C-11-methionine, Tl-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin were used to evaluate the cellular uptake in MCF-7 cells. MCF-7 cells were cultured in multi-well plates. Wells were divided into DMSO exposure control group, and paclitaxel exposure group. The exposure durations of paclitaxel with 10 nM or 100 nM were 2 h, 6 h, 12 h, 24 h, and 48 h. RESULTS: Viable cell fraction was reduced as the concentration and exposure time of paclitaxel increased. After 10 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was not reduced significantly, irrespective of exposure time and viable cell fraction. After 100 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was enhanced significantly irrespective of viable cell fraction. The peak uptake was observed in experimental groups with paclitaxel exposure for 6 to 48 h according the type of radiopharmaceutical. When the cellular uptake was adjusted for the viable cell fraction and cell count, the peak cellular uptake was observed in experimental groups with paclitaxel exposure for 48 h, irrespective of the type of radiopharmaceutical. CONCLUSION: The cellular uptake of F-18-fluorodeoxyglucose, C-11-methionine, Tl-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin did not reflect viable cell number in MCF-7 cells after paclitaxel exposure for up to 48 h.

Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein / 대한핵의학회잡지

PURPOSE: 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of 99mTc-MIBI and 99mTc-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. MATERIALS AND METHODS: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. RESULTS: RT-PCR, western blot analysis of the cells and immunochemical staining revealed selective expression of Pgp and MRP for HCT15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p< 0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. CONCLUSION: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

Diagnostic Accuracy of Quantitative Scintimammography Using Tc-99m Tetrofosmin according to ROC Curve Analysis for Breast Cancer / 한국유방암학회지

PURPOSE: Tc-99m Tetrofosmin is a new alternative to Tc- 99m MIBI for nuclear breast imaging. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the feasibility of Tc-99m Tetrofosmin quantitative scintimammography (SMM) (qSMM) and to compare with previously reported Tc-99m MIBI qSMM data [J Kor Surg 1999;57(5):638-644)]. METHODS: Prone anterior, lateral planar and supine SPECT images were taken from 135 cases in 131 female patients (mean ages=44 yr) with breast mass (size> or =0.2 cm) after 30mCi intravenous injection of Tc-99m Tetrofosmin. 70 malignant and 65 benign lesions were histologically proven. Three regions of interest (ROIs) were drawn over designated areas: the Lesion (L), the Normal breast opposite the lesion (NL) and the right Chest wall (CW). L/NL and L/CW ratios on both the SPECT and the planar images were analyzed. RESULTS: ROC curve analysis revealed that the planar L/NL ratio and the SPECT L/NL and L/CW ratios had higher diagnostic accuracy for detecting breast cancer than he planar L/CW ratio did (P<0.05). The qSMM (mean), which is an arithmetic mean of the planar L/NL ratio, the SPECT L/NL ratio and the SPECT L/CW ratio, the sensitivity, the specificity, accuracy and area under curve (AUC) were 82.9%, 81.5%, 82.2% and 0.879 respectively. Presence of axillary lymph node metastasis showed a slightly higher qSMM (mean) value (2.79 {n=23} vs 2.75 {n=27} P=0.06). These are comparable with previously reported Tc-99m MIBI qSMM data of 84.4%, 76.6%, 81.0% and 0.847 respectively, and the presence of axillary lymph node metastasis showed a higher qSMM(mean) value (4.09 {n=17} vs 3.09 {n=28}, P=0.06) [J Kor Surg 1999; 57(5):638-644)]. CONCLUSION: Tc-99m Tetrofosmin qSMM (mean) is a useful and objective method for differentiating malignant from benign breast lesion and has the comparable diagnostic accuracies of Tc-99m MIBI qSMM.

Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells / 대한핵의학회잡지

PURPOSE: Cellular uptake of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance (MDR) by p-glycoprotein (Pgp) or multidrug related protein (MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. MATERIALS AND METHODS: Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562 (Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 micro M at 1x10 (6) cells/ml at 37degrees C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. RESULTS: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562 (Adr) cell at a concentration of 100 micro M and the maximal increase at 50 micro M was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 micro M. With a concentration of 200 micro M verapamil, MIBI and TF uptakes in K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10 micro M, but were also decreased with verapamil higher than 10 micro M, resulting 40% and 5% of baseline at 50 micro M. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 micro M. CONCLUSION: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

Comparison of the Uptakes of 99mTc-sestamibi and 99mTc-tetrofosmin in Cancer Cell Lines Expressing Multidrug Resistance / 대한핵의학회잡지

PURPOSE: Cellular uptakes of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin into cancer cell lines expressing multidrug resistance (MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. MATERIALS AND METHODS: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562 (Adr) and vincristine-resistant K562 (Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at 1x10 (6) cells/ml incubated at 37 degrees C. Radioactivity in supernatants and pellets were measured with gamma well counter. RESULTS: The cellular uptakes of MIBI and tetrofosmin in K562 (Adr) and K562 (Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562 (Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562 (Vcr) cells. Coincubation with verapamil resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562 (Adr) cell by 14.3- and 8-fold and by K562 (Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyclosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562 (Adr) cell by 44- and 13-fold and by K562 (Vcr) cell by 18.8- and 11.8-fold in maximum, respectively. CONCLUSION: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for detecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.

Comparison of the Uptakes of Tc-99m MIBI and Tc-99m Tetrofosmin in A549, an MRP-expressing Cancer Cell, In Vitro and In Vivo / 대한핵의학회잡지

PURPOSE: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. MATERIALS AND METHODS: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at 100 umM of verapamil (Vrp), 50 umM of cyclosporin A (CsA) and 25 umM of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 60 min at 37degrees C, using single cell suspensions at 1x10 (6) cells/ml. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). RESULTS: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. CONCLUSION: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

99mTc-tetrofosmin, 131I Whole Body Scan and Thyroglobulin in Detecting Differentiated Thyroid Carcinoma Metastases

PURPOSE: The purpose of this study was to assess the detectability of differentiated thyroid carcinoma metastases by 99mTc-tetrofosmin and to compare these results with a 131I whole body scan (131I WBS). The results of two scans were also compared with the T4 off-thyroglobulin (Tg) concentration. METHODS: A prospective study was performed on 43 patients (40 females, 3 males) with differentiated thyroid carcinomas (41 papillary, 2 follicular) having undergone a total thyroidectomy, and received 100~200 mCi (3,700~7,400 MBq) of radioiodine for ablation of residual thyroid tissue, or treatment of metastasis. All patients (n=43) had a 99mTc- tetrofosmin scan, and a 131I WBS following the discontinuation of thyroid hormone replacement. The T4 off-Tg level was checked immediately prior to the radioiodine therapy, with T4 off-Tg levels above 20 ng/ml defined as positive for metastasis or a remnant disease. RESULTS: Cervical metastases were considered in 6 patients and distant metastases in 7, based on the clinical, radiological, and histopathological findings. The 131I WBS (70.2%) was much more sensitive than the 99mTc-tetrofosmin scan (29.8%) in demonstrating the residual thyroid tissue following surgery. The 131I WBS revealed cervical metastases in 3 of the 6 patients, but only 2 of the 6 were revealed by the 99mTc-tetrofosmin scan. Of the 3 patients with negative 131I WBS, two were detected by the 99mTc-tetrofosmin scan. The sensitivities of the 131I WBS and 99mTc-tetrofosmin scan in diagnosing distant metastases were comparable (71%, and 57% respectively), but in 2 patients with negative 131I WBS, the 99mTc-tetrofosmin revealed distant metastases. The specificities of the 131I WBS and 99mTc-tetrofosmin scan were not comparable (100%, 97%, respectively) in the diagnosis distant metastases. The mean T4 off-Tg level of the patients with cervical or distant metastases was 317 ng/ml, with a sensitivity and specificity of 100%, and 83% respectively. In the patients with a T4 off-Tg level above 50 ng/ml, the two scans and clinical studies could not reveal any metastases in 3 of the patients. CONCLUSION: Although the specificity of the 99mTc-tetrofosmin scan was slightly lower than that of the 131I WBS, it is a useful tool for detecting cervical or distant metastases in differentiated thyroid carcinomas and does not require prior withdrawal from thyroid hormones. Therefore the concomitant use of a 99mTc-tetrofosmin scan, a 131I WBS and Tg, is more effective in detecting metastases in differentiated thyroid carcinomas.

Comparison of Tc-99m-Tetrofosmin and Tc-99m-MIBI Scintimammography in Differential Diagnosis of Breast Mass / 대한핵의학회잡지

PURPOSE: Tc-99m-MIBI (MIBI) and Tc-99m-Tetrofosmin (TF) are commonly used for scintimammography (SMM). We compared the diagnostic ability of SMM using Tc-99m-MIBI and Tc-99m-TF for the differential diagnosis of breast mass. MATERIALS AND METHODS: The study subjects were comprised of 123 breast lesions and 86 normal breasts of 114 patients who underwent SMM. Bilateral prone images and anterior supine images were obtained at 5 minutes and 1 or 3 hours after intravenous injection of 740 MBq of either MIBI or TF. Sizes of tumors were not significantly different between the MIBI and TF groups. First, two observers independently read the SMM without clinical information (1st interpretation), then read again with information about mass location (2nd interpretation). Sensitivity and specificity of each radiopharmaceutical for the diagnosis of breast cancer were evaluated in terms of image acquisition time, tumor size, and location. RESULTS: The SMM showed a good agreement between two observers for 1st and 2nd interpretation, except for TF SMM at 3 hr. For the first interpretation, the sensitivities at 5 min, 1 hr, and 3 hr were not significantly different between MIBI and TF SMM (81.6%, 80.0%, 60.9% in MIBI vs. 88.9%, 80.6%, 42.9% in TF), although the senstivities of 3 hr images were significantly lower than 5 min images in both MIBI and TF SMM. The specificity of TF at 5 min was superior to that of MIBI (81.5%, 90.0%, 82.9% in MIBI vs. 96.7%, 100%, 90.0% in TF, p<0.01 MIBI vs. TF at 5 min). For the second interpretation with information of mass location, the sensitivities at 3 hr images were significantly lower than 5 min images (86.8%, 86.7%, 78.3% in MIBI vs. 88.9%, 93.5%, 57.1% in TF) between MIBI and TF SMM. However, there was no significant difference in the specificity (60.0%, 53.8%, 75.0% for MIBI vs. 86.7%, 100%, 100% for TF). MIBI and TF SMM showed lower sensitivities for the tumors with less than 1 cm than tumors with more than 1 cm. However, the location of tumors did not influence the sensitivity and specificity between MIBI and TF SMM. CONCLUSION: The ability for the differential diagnosis of breast tumor is similar between MIBI and TF SMM, and delayed image is not necessary. TF may be better than MIBI considering the specificity of SMM without clinical information and labeling convenience.

Diagnostic Usefulness of Tc-99m Tetrofosmin Scintimammography in Patients with Primary Breast Cancer / 대한핵의학회잡지

PURPOSE: The purpose of this study was to evaluate the diagnostic usefulness of scintimammography performed with Tc-99m tetrofosmin in the detection of primary breast cancer. MATERIALS AND METHODS: Sixty-one patients underwent Tc-99m tetrofosmin scintimammography, plain-filrn mammography and ultrasonography. After intravenous injection of Tc-99m tetrofosmin (740 MBq), prone lateral and anterior scintimammograms were obtained. Scintimammogram was visually interpreted as positive, probably positive, probably negative and negative for malignancy. The tumor to background count ratio (T/B) was measured at 5 minutes and 1 hour. Plain-film mammogram was interprcted as one of 5 categories. Final diagnosis was achieved by surgical histology (58/61) or fine needle aspiration (3/61). Of 61 patients, 44 had cancer and 17 had benign lesion. Tumor size of malignant and benign lesions on ultrasonogram were 2.51+/-1.30 cm (range 1-8 cm), 2.50+/-1.35 cm (range 0.96-6 cm), respectively. RESULTS: The sensitivity of plain-film mammography was 88.6%, specificity 58.8%, positive predictive value 84.7%, and negative predictive value 66.7%. The sensitivity of Tc-99m tetrofosmin scintimammography was 90.9%; specificity, 88.2%; positive predictive value, 94.9%; negative predictive value, 78.9%. Of 25 patients with indeterminate degree of suspicion for malignancy on plain-film mammogram, 23 were correctly diagnosed by scintimamography. The T/B at 5 minutes and 1 hour were 3.78+/-2.21, 3.25+/-1.80 respectively. The T/B was decreased significantly at 1 hour (p<0.001). CONCLUSION: Tc-99rn tetrofosrnin scintimammography was useful diagnostic procedure in the detection of primary breast cancer, especially in patients with indeterminate degree of suspicion for malignancy on plain-film mammogram.

Diagnostic Value of Dipyridamole Tc-99m Tetrofosmin SPECT for Detection of Coronary Artery Disease

Background and Objects: Tc-99m tetrofomsin is a recently developed myocardial perfusion agent. We examined the diagnostic accuracy of dipyridamole Tc-99m tetrofosmin SPECT. MATERIALS AND METHOD: 61 patients underwent one-day rest/dipyridamole Tc-99m tetrofosmin SPECT. 26 patients had history of myocardial infarction. Coronary angiography, performed within 1 week after SPECT study, revealed normal coronary arteries or insignificant coronary artery stenosis in 19 and 22 patients (when considering > or = 50% or > or = 70% reduction of luminal diameter as significant stenosis). RESULTS: Number of male was 39 (63.9%) and mean age was 59 (range 32 - 84). The diagnostic accuracy of dipyridamole Tc-99m tetrofosmin SPECT for detection of coronary artery disease (> or = 50% and > or = 70% coronary artery stenosis, respectively) was as follows: sensitivity 90.5%, 90.0%, specificity 73.7%, 66.7%, positive predictive value 88.4%, 83.7%, negative predictive value 77.8%, 77.8% and predictive accuracy was 85.2%, 81.9% respectively. The overall sensitivity and specificity of dipyridamole Tc-99m tetrofosmin SPECT for detection of individual coronary stenosis (> or = 50% and > or = 70% coronary stenosis by coronary angiography) were 64.6%, 64.1% and 86.4%, 85.7% respectively. In patients without myocardial infarction, sensitivity 76.5%, specificity 76.5%, positive predictive value 83.3%, negative predictive value 76.5% and predictive accuracy was 80.0%. CONCLUSION: One-day rest/stress dipyridamole Tc-99m tetrofosmin myocardial SPECT is a useful noninvasive method for detection of coronary artery disease.