Comparative 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin uptake in human soft tissue sarcoma cell lines

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), ^99mTc-tetrofosmin and ^99mTc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37°C, 32°C and 22°C with ^99mTc-MIBI, ^99mTc-tetrofosmin and ^99mTc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of ^99mTc-MIBI, ^99mTc-tetrofosmin and ^99mTc-furifosmin was temperature dependent. The kinetics of uptake of ^99mTc-MIBI and of ^99mTc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. ^99mTc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of ^99mTc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of ^99mTc-MIBI, ^99mTc-tetrofosmin and ^99mTc-furifosmin is dependent on cellular metabolic activity.     

Comparison of uptake of99mTc-MIBI,99mTc-tetrofosmin and99mTc-012 into human breast cancer cell lines

Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI),^99mTc-tetrofosmin and^99mTc-Q12 were all introduced for myocardial imaging but found additional applications as they are taken up by different tumours, enabling imaging of these lesions in patients. The aim of this study was to compare the uptake characteristics of these compounds in vitro in the human adenocarcinoma breast cell lines MCF-7 and ZR-75. It was shown that^99mTc-MIBI had the highest cellular uptake (15.9%±0.5% dose/mg protein after 60 min in MCF-7, and 14.2%±0.4% dose/mg protein in ZR-75), followed by^99mTc-tetrofosmin (6.8%±0.6% dose/mg protein in MCF-7, and 8.2%±0.2% dose/mg protein in ZR-75) and^99mTc-Q12 (3,2%±0. I% dose/mg protein in MCF-7, and 3.5%±0.3% dose/mg protein in ZR-75 cells). For all three compounds tenfold differences in specific activity did not influence total cell-associated radioactivity. Uptake of^99mTc-MIBI and^99mTc-tetrofosmin was obviously lower at 4° C than at 37° C, whereas^99mTc-Q12 uptake showed only slight temperature dependence. When uptake was compared in cells grown to different cell densities (1 mg/ml cellular protein versus 0.3 mg/ml), no differences in uptake were detected when uptake was corrected for the amount of cellular protein present in the dishes. Furthermore, for all compounds it was shown that cellular radioactivity decreased rapidly after washing. Apart from the differences in cellular uptake of the three compounds after 60 min, no differences in residual cellular radioactivity after washing were found between the different compounds when expressed as a percentage of their 60-min uptake, suggesting that the efflux process of the radiolabelled compounds was similar. The differences in cell-associated activity after 60 min were thus presumably caused by differences in uptake. It was concluded that of the Tc-labelled compounds tested,^99mTc-MIBI had the highest cellular retention in both human breast tumour cell lines. However, for imaging in vivo not only radioactivity in the target organ is important, but also the ratio of radioactivity in the target versus that in the background. Therefore, further studies in vivo need to be performed to investigate which compound is the optimal imaging agent     

201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts

Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc-furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and 99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc-tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc-MIBI and 99mTc-tetrofosmin.     

Uptake of 99mTc-MIBI and 99mTc-tetrofosmin into malignant versus nonmalignant breast cell lines.

The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared. METHODS: At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed. RESULTS: The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar. CONCLUSION: In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease.     

Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

Tc-99m MDP uptake in soft tissue extraskeletal metastasis from osteogenic sarcoma

A bone scan in a patient with proved osteogenic sarcoma of the tibia showed intense focal uptake in the gluteal region on the side of his cancer. This was proved to be a metastasis in the muscle.     

99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation of the relationship between99mTc-MIBI uptake and P-alvcoprotein expression in tumour tissue

Technetium-99m hexakis-2-methoxyisobutyl-isonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression. Two scintigraphic patterns - TI(+)/MIBI(–) in primary tumour and TI(+)/MIBI(+) in metastatic tumour — were observed, suggesting high- and low-level PGP expression, respectively. Immunochemical study for PGP revealed strong staining of the primary tumour cells. This case clinically validates the previously suggested relationship between^99mTc-MIBI uptake and PGP expression.     

99mTc-tetrofosmin uptake in bone metastases from breast cancer

^99mTc-tetrofosmin myocardial imaging was performed in a 62-year-old woman who had undergone standard radical mastectomy for right breast cancer 6 years ago. Although the result was negative for the ischemic heart disease, it showed abnormal accumulation corresponding to the bone metastases in the spine. We believe that^99mTc-tetrofosmin imaging is helpful in detecting bone metastases from breast cancer.     

Size and P-glycoprotein expression limit 99mTc-tetrofosmin uptake in parathyroid adenomas

The purpose of this study was to retrospectively evaluate (99m)Tc-tetrofosmin (Tc-TF) uptake in large parathyroid adenomas and to compare the results with their expression of multidrug resistance (MDR)-mediated, 170 kDa, P-glycoprotein (Pgp). Twenty patients with large parathyroid adenomas (larger than 1.5 g), who had undergone early and delayed (10 min and 2 h) Tc-TF parathyroid imaging before operation, were enrolled in this retrospective study. Immunohistochemical analyses were performed on multiple, non-consecutive sections of the 20 parathyroid adenomas and 40 normal control specimens (20 normal parathyroid glands and 16 normal thyroid specimens) to detect Pgp expression. Tc-TF parathyroid imaging accurately localized 17 large parathyroid adenomas, but not the remaining three. The 17 parathyroid adenomas with significant Tc-TF uptake in delayed (2 h) parathyroid images revealed negative Pgp expression, but the three adenomas without significant Tc-TF uptake, as well as 20 normal parathyroid glands and 20 normal thyroid specimens, revealed positive Pgp expression. Therefore, not only the size, but also the expression of Pgp, limited the sensitivity of Tc-TF parathyroid imaging to localize parathyroid adenomas before operation.     

99mTc-MIBI imaging of AIDS-related Kaposi's sarcoma in the lungs

OBJECTIVE: Pulmonary Kaposi's sarcoma (KS) occurs in more than 10% of patients with acquired immunodeficiency syndrome (AIDS) and has a high mortality rate. Prompt detection, diagnosis, and treatment reduce patient morbidity and mortality. The objective of this study was to determine the efficacy of 99mTc-hexakis-2-methoxy isobutyl isonitrile (99mTc-MIBI) imaging in detecting pulmonary AIDS-related KS. METHODS: 99mTc-MIBI imaging was performed on 72 human immunodeficiency virus-seropositive patients with bronchoscopic diagnosis of pulmonary KS (36 patients), pneumonia (22), normal tracheo-bronchial tree (11), lymphoma (2), and bronchogenic carcinoma (1). Lung uptake and lymph node detection in KS were compared on planar and single photon emission computed tomography (SPECT) scans. RESULTS: The lung/myocardium ratios on the 1-h planar images were significantly higher in KS and normal lungs than opportunistic infection. Using the lung/myocardium ratio of 1 as cutoff, the sensitivity, specificity, and accuracy of the 1-h planar images for detecting pulmonary KS were 75, 57.58, and 66.67%, respectively. Abnormal lymph node uptake, pleural/pericardial effusions, and ascites were detected more readily on SPECT. CONCLUSION: Planar 99mTc-MIBI imaging has moderate sensitivity, specificity, and accuracy for detecting pulmonary KS. SPECT is more effective in detecting abnormal lymph nodes, pleural/pericardial effusions, and ascites. 99mTc-MIBI SPECT followed by planar imaging at 40-60 min can be useful in assessing pulmonary KS.     

~(99m)Tc-YIGSR与~(99m)Tc-MIBI肿瘤细胞摄取比较研究

目的利用肿瘤细胞表面含有大量层粘素受体,而且能与层粘素特异性结合机制,研究99mTc-YIGSR(层粘蛋白-小分子肽)作为一种新型的肿瘤显像剂,在埃氏腹水瘤细胞(EAC)中的摄取并与MIBI进行比较.方法①99mTc-MAG3-YIGSR 探针的制备利用S-已基-琥铂酰亚胺-巯已甘肽(S-Acetly-NH3-MAG3)作为螯合剂,在适当还原剂作用下,将99mTc标记到层粘素-YIGSR上,用Sphadex G10凝胶柱纯化,根据放射性计数及280nm紫外吸光值合并各峰管,利用纸层析进行放射性化学纯度分析.②细胞培养及细胞存活率测定EAC在含小牛血清的1640细胞培养液中悬浮培养,用台盼兰排除法计数活细胞.③细胞动力学研究用放射性核素示踪法研究EAC在37℃和22℃时对99mTc-YIGSR及99mTc-MIBI的摄取.结果①99mTc-YIGSR标记率为(62±3)%,放化纯为95%,99mTc-MIBI标记率为(96±2)%,放化纯为98%.②细胞存活率随孵育时间延长而下降,实验前细胞存活率为96%±1%,孵育2h细胞及3h存活率分别为(96±1)%及(90±2)%,均在85%以上符合实验要求.③37℃ 60min时,EAC对99mTc-YIGSR及99mTc-MIBI的摄取峰值分别为(43.16±2.4)%和(24.4±1.8)%;在22℃时EAC摄取峰值分别为(26.5±2.1)%和 (9.47±1.9)%.结论在相同条件下EAC对99mTc-YIGSR摄取峰值高于99mTc-MIBI,更适用于肿瘤显像,在临床上具有潜在的应用价值.     

Incidental pathologic extracardiac uptake of 99mTc-tetrofosmin in myocardial perfusion imaging

Technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion studies have incidentally detected various extracardiac abnormalities. The interpretation of these findings may be essential for early diagnosis and treatment of important diseases. We present a rare case of a mediastinal thymoma incidently detected during myocardial perfusion imaging. A 60 year-old woman, with precardiac symptoms of possible myocardial ischemia, underwent a (99m)Tc-TF stress-rest single photon emission tomography test. Intense uptake of the radiotracer in the left paracardiac area, was observed. The computerized tomography and the magnetic resonance imaging tests revealed a mass in the left lower anterior mediastinal area. Biopsy and subsequent histology showed that this mass was a thymoma.     

Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance

An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and²⁰¹Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%±0.5% vs 3.1%.0.6%;P <0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%;P <0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2±81.1 nmoUmg protein to 17.6±4.4 nmol/mg protein;P <0.001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%±0.5% and 5.93%±1.7%, respectively;P >0.1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.     

Correlation between 99mTc-MIBI uptake and angiogenesis in MIBI-positive breast lesions

This study was undertaken to assess the correlation between the degree of accumulation and the washout of 99m technetium methoxyisobutylisonitrile ((99m)Tc-MIBI) and angiogenesis in MIBI-positive breast lesions. Twenty-eight patients (mean age, 51+/-11 years) with 31 breast lesions who underwent scintimammography were studied. Anterior, left and right prone lateral images were obtained 20 min and 3 h after the injection of 740 MBq (99m)Tc-MIBI. All breast lesions showed increased (99m)Tc-MIBI uptake. Early and delayed tumor to background activity ratios (T/BG) and washout index (early tumor uptake-delayed tumor uptake divided by early tumor uptake) were calculated. Vascular endothelium was immunohistochemically labeled using a biotinylated monoclonal antibody directed against the factor-VIII-associated antigen using standard biotin-avidin technique. Angiogenesis was evaluated by assessing the vascular surface density (VSD) and the microvessel number (NVES) within 10 randomly chosen areas. All pathological data were compared with early and delayed T/BG activity ratios and washout index of (99m)Tc-MIBI. Statistical analysis was performed using Spearman correlation test. There was no statistically significant correlation between the degree of angiogenesis and early T/BG (r = .287, P > .05 with VSD, r = .351, P > .05 with NVES), delayed T/BG (r = .277, P > .05 with VSD, r = .315, P > .05 with NVES) and the washout index (r = .268, P > .05 with VSD, r = .285, P > .05 with NVES) of (99m)Tc-MIBI in all breast lesions. There was no statistically significant correlation between the degree of angiogenesis and early T/BG (r = .235, P > .05 with VSD, r = .356, P > .05 with NVES), delayed T/BG (r = .181, P > .05 with VSD, r = .285, P > .05 with NVES) and the washout index (r = .158, P > .05 with VSD, r = .187, P > .05 with NVES) of (99m)Tc-MIBI in 24 invasive breast lesions. No statistically significant correlation was found between the degree of angiogenesis and early T/BG (r = -.036, P > .05 with VSD, r = -.107, P > .05 with NVES), delayed T/BG (r = -.500, P > .05 with VSD, r = -.429, P > .05 with NVES), but there was a high correlation between angiogenesis and the washout index (r = .893, P < .05 with VSD, r = .964, P < .05 with NVES) of (99m)Tc-MIBI in seven noninvasive breast lesions. Amount of (99m)Tc-MIBI uptake in breast lesions is dependent on several factors. Our study indicates that early and delayed (99m)Tc-MIBI uptakes in MIBI-positive breast lesions are not related to angiogenesis in both invasive and noninvasive breast lesions. But washout index of (99m)Tc-MIBI in noninvasive breast lesions is highly correlated with angiogenesis. (99m)Tc-MIBI scintigraphy does not seem to be able to indicate angiogenic property of invasive breast lesions.