Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma.

Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib.

In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue.

INTRODUCTION: Noninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of (99m)Tc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy. METHODS: Ten million cells of SVF were labeled with (99m)Tc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of (99m)Tc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H2DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1. RESULTS: An encouraging labeling efficiency of 33% was observed with (99m)Tc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays. CONCLUSION: (99m)Tc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with (99m)Tc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.

Growth inhibitory and apoptosis-inducing effects of xanthohumol, a prenylated chalone present in hops, in human prostate cancer cells.

Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstrated that prostate cancer cells are highly sensitive to XN at a concentration range of 20-40 µM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of annexin V-FITC, cleavage of PARP-1, activation of procaspases -3, -8, and -9, mitochondrial depolarization and release of cytochrome c from mitochondria. Induction of apoptosis by XN was associated with the inhibition of prosurvival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2 and survivin. These studies provide a rationale for clinical evaluation of XN for the treatment of hormone-refractory metastatic prostate cancer.

Imaging Mouse Prostate Gland by 3 Tesla Clinical MRI System.

In vivo detection of prostate tumor in animal model will facilitate the investigations that deal with the efficacy of different treatment strategies in different experimental settings. Recently higher field strength dedicated animal MRI system has been used successfully to detect mouse prostate glands and its lesions, however, usefulness of clinical system has not been utilized to its fullest extent. In this short communication we show the advantages and disadvantages of different in vivo imaging parameters of MRI to acquire images of the mouse prostate gland using clinical strength MRI systems.

Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging.

Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside.

Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: relationship between relaxivities, electrostatic forces, and chemical composition.

The purpose of this study was to investigate the changes in electrostatic and magnetic resonance (MR) properties observed when MR contrast agents (CAs) (Feridex, MION-46L, or G5-dendrimer-DOTA-Gd) are combined with transfection agents (TAs) under various conditions for use as a CA-TA complex basis for cellular labeling and MRI. CAs were incubated with various classes of TAs for 0-48 hr in solutions of varying concentrations and pH values. NMR relaxation rates (1/T(1), 1/T(2)), MRI and zeta potential (ZP) of CA-TA solutions were measured. TAs decreased the 1/T(1) and 1/T(2) of G5-DOTA-Gd, Feridex, and MION-46L by 0-95%. Altering the pH of G5-DOTA-Gd-TA decreased the T(1)-weighted signal intensity (SI) on MRI from 0 to 78%. Measured ZP values for G5-DOTA-Gd, Feridex, and MION-46L were -51, -41, and -2.0 mV, respectively. The TA LV had a negative ZP, while the other TAs had ZPs ranging from +20 to +65 mV. The alteration of the ZP and NMR relaxivities of the MR CAs, Feridex, MION-46L, and G5-DOTA-Gd by TAs has been demonstrated. These results enhance our understanding of the relationship between electrostatic and MR properties.

Effects of extracellular Na+ and Ca2+ ions and Ca2+ channel modulators on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin in tumour cells.

Our aim was to determine whether the Ca2+ ion or cell membrane Ca2+ and Na+/Ca2+ ion transport systems are involved in maintaining the cell-associated activity of technetium-99m-hexakis-methoxy-isobutyl-isonitrile (99mTc-MIBI) and technetium-99m-ethylene-bis[bis(2-ethoxyethyl)phosphin] (99mTc-tetrofosmin) in tumour cell lines. The cell-associated activities of 99mTc-MIBI and 99mTc-tetrofosmin were assessed in various buffers, with or without Na+ and/or with different concentrations of Ca2+, in Lewi's murine lung cell carcinoma and human glioma cell lines. Different Ca2+ channel modulators, such as verapamil, flunarizine and 3,4-dichlorobenzamil (DCB), were used to assess the effect of Ca2+ channels on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin. Despite significant differences between cell lines, the cell-associated activity of 99mTc-MIBI was higher in buffers without extracellular Ca2+ and Na+. The cell-associated activity of 99mTc-MIBI was significantly lower in all buffers containing high concentrations of Ca2+ in both cell lines. The cell-associated activity of Tc-tetrofosmin was also significantly higher in buffers without Ca2+, and was significantly decreased in buffers with high concentrations of Ca2+. All modulators significantly increased the cell-associated activity of 99mTc-MIBI in both cell lines in all buffers. All modulators increased the cell-associated activity of 99mTc-tetrofosmin, particularly in buffers containing Ca2+. The cell-associated activities of both 99mTc-MIBI and 99mTc-tetrofosmin may be dependent on verapamil-, flunarizine- and DCB-sensitive Ca2+ channels.

Duct-penetrating sign at MRCP: usefulness for differentiating inflammatory pancreatic mass from pancreatic carcinomas.

PURPOSE: To define the duct-penetrating sign at magnetic resonance (MR) cholangiopancreatography (MRCP) and to assess the usefulness of this sign for distinguishing an inflammatory pancreatic mass (IPM) from a conventional pancreatic carcinoma (CPC) compared with arterial phase computed tomography (hereafter, CT) and arterial phase MR imaging (hereafter, MR imaging). MATERIALS AND METHODS: MRCP, CT, and MR images were compared by means of receiver operating characteristic (ROC) analysis for 11 IPMs and 43 CPCs. With the MRCP images, a morphologic classification of the main pancreatic duct (MPD) was attempted for all lesions. On the basis of this classification and the enhancement patterns of a lesion, all readers graded the presence of IPM or CPC on a five-point scale for all images. RESULTS: On the MRCP images, the morphologic characteristics of the MPD were nonobstruction for IPM (28 of 33, 85%) and obstruction or irregular stenosis for CPC (124 of 129, 96%). At ROC analysis among all the techniques, MRCP images had the highest value (0.98) for significant areas under the ROC curve (CT, 0.84; MR, 0.76) (P <.001). For the duct-penetrating sign in the broad sense (nonobstructed MPD) and the sign in the narrow sense (only normal MPD), the sensitivity, specificity, and accuracy for diagnosis of IPM were 85%, 96%, and 94%, respectively, and 36%, 100%, and 87%, respectively. CONCLUSION: The duct-penetrating sign on MRCP images was more helpful to distinguish IPM from CPC than were the enhancement patterns on CT and MR images.

Brain perfusion measured by flow-sensitive alternating inversion recovery (FAIR) and dynamic susceptibility contrast-enhanced magnetic resonance imaging: comparison with nuclear medicine technique.

The aim of this study was to compare cerebral perfusion images and regional cerebral blood flow (rCBF) of SPECT study with the images and regional intensity of relative cerebral blood flow (CBF) images acquired by contrast-enhanced perfusion MR imaging (pMRI) and flow-sensitive alternating inversion recovery (FAIR). Twelve patients with various cerebral diseases were underwent I-123-IMP SPECT, pMRI, and FAIR studies to measure rCBF. A total of 12 regions of interest (ROI) were created over cerebrum and cerebellum to acquire the corresponding rCBF from I-123-IMP study and regional average signal intensity from CBF images of pMRI and FAIR studies. Left-to-right (L/R) and cerebral-to-cerebellar (CCR) ratios were created from the rCBF of I-123-IMP and signal intensity of CBF images of pMRI and FAIR. Image quality of FAIR was the poorest among all; however, CBF images of pMRI and FAIR images show comparatively decreased intensity at the corresponding site of decreased perfusion on I-123-IMP images. Both FAIR and pMRI images showed high intensity along the sinuses, choroid plexus, and large vessels in sulci. No significant correlation was found among all imaging modalities. But L/R ratio of I-123-IMP showed significant correlation with those of pMRI and FAIR, but for CCR, significant correlation was observed only between I-123-IMP and FAIR. Perfusion images of both pMRI and FAIR may produce images comparable to SPECT study. But to calculate absolute CBF more easy-to-apply and accurate algorithms are needed to overcome the artifacts from large vessels.

Evaluation of crossed cerebellar diaschisis in 30 patients with major cerebral artery occlusion by means of quantitative I-123 IMP SPECT.

Quantitative crossed cerebellar diaschisis (CCD) and the correlation with a reduction in supratentorial regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) were investigated in clinically stable patients with major cerebral artery occlusion by the iodine-123-N-isopropyl-p-iodoamphetamine (I-123 IMP) single photon emission computed tomography (SPECT) method. Thirty patients with major cerebral artery occlusion underwent SPECT by the I-123 IMP autoradiographic method. Regional CBF was measured in the cerebral hemisphere, frontal and parietal lobes, temporo-parietal lobe, and cerebellum both at rest and after administration of acetazolamide. Eighteen of 30 patients (60%) had CCD. CCD was significantly related to magnetic resonance imaging evidence of infarction. Quantitative CCD was 17% and the CVR in the cerebellum was preserved in patients with CCD. There was a significant difference in CBF and CVR between the affected and normal sides in all regions of interest in the patients without CCD [CBF (ml/100 g/min): hemisphere (H), normal side (N): 31.4 +/- 6.8, affected side (A): 27.5 +/- 7.4; p < 0.05. CVR: H, N: 0.56 +/- 0.38, A: 0.42 +/- 0.18; p < 0.01]. CCD is common in patients with major cerebral artery occlusion, and quantitative I-123 IMP SPECT is helpful in detecting CCD in clinically stable patients with occlusion of major cerebral arteries.

Simultaneous display of MRA and MPR in detecting vascular compression for trigeminal neuralgia or hemifacial spasm: comparison with oblique sagittal views of MRI.

A new technique, simultaneous display of magnetic resonance angiography (MRA) and multiplanar reconstruction (MPR), was performed by a workstation to identify the involved vessels in patients with trigeminal neuralgia (TN) or hemifacial spasm (HFS), and the results were compared with those of oblique sagittal MRI technique. Twelve patients with either HFS or TN were prospectively assessed by simultaneous display of MRA and MPR, and oblique sagittal techniques, to point out the neurovascular compression and to identify the involved vessels. Three-dimensional (3D) time-of-flight (TOF) spoiled gradient-echo (SPGR) images were acquired to create MRA and MPR. Oblique sagittal views were also created and displayed on films. A total of 15 vessels in 12 patients were identified as compressing vessels during surgery. Simultaneous display of MRA and MPR technique pointed out the presence of vessels at and/or around root entry/exit zone (REZ) in all 12 patients, but proper identification by the name of the individual vessel was correct in 13 of 15 cases. However, oblique sagittal technique indicated the presence of vessels at and/or around REZ in 11 patients, but only 8 of 14 vessels were correctly identified. Our new method, simultaneous display of MRA-MPR, facilitated correct identification of the involved vessels compared with the oblique sagittal view method.

Various imaging modalities for the detection of salivary gland lesions: the advantages of 201Tl SPET.

The aim of this study was to compare dual-isotope (99Tc(m) and 201Tl) SPET imaging with computed tomography (CT) and magnetic resonance imaging (MRI) in the differentiation of various lesions of the major salivary glands. Twenty-two patients underwent dual-isotope SPET imaging, of whom 12 also had CT and 15 also had an MRI study. The uptake ratio and retention index for 99Tc(m) and 201Tl were calculated by drawing regions of interest on the involved and normal glands. Both CT and MRI were interpreted by two radiologists. All malignant tumours were detected by all three modalities. Warthin's tumours were detected by dual-isotope SPET imaging; however, MRI failed to differentiate Warthin's tumour from pleomorphic adenoma. Of 13 other benign tumours, dual-isotope SPET correctly diagnosed 12. Of 16 tumours showing a cold defect on the 99Tc(m) images, parametric analysis with 201Tl gave an accuracy of 94%, whereas CT gave an accuracy of 70-90%. MRI was 73-91% accurate in differentiating between benign (Warthin's) and malignant tumours. We believe that dual-isotope SPET imaging (99Tc(m) and 201Tl), together with semi-quantitative analysis, is the method of choice for differentiating between various lesions of the major salivary glands.

Detection of hepatocellular carcinoma and its metastases with various pulse sequences using superparamagnetic iron oxide (SHU-555-A).

BACKGROUND: To identify the most useful combinations of various pre- and postcontrast magnetic resonance (MR) image sequences in detecting hepatocellular carcinoma (HCC) and its intrahepatic metastases before and after injection of SHU-555-A. METHODS: Thirty-eight lesions in 16 patients were evaluated before and after administration of SHU-555-A by using fast spin echo (FSE), gradient echo (GRE), and echo planar (EP) imaging sequences using a 1.5-Tesla superconducting MR system. The signal intensity ratio (SIR) and contrast-to-noise ratio (CNR) of the lesions, signal-to-noise ratios, and other parameters were calculated. RESULTS: Tumors were better detected after injection of SHU-555-A on all pulse sequences except on out-of-phase T1-weighted (T1W)-GRE sequences. Tumor detectability was higher for precontrast EP imaging and T2*-weighted (T2*W)-GRE sequences, whereas detectability at postcontrast was higher for T2*W-GRE, proton-density-weighted-FSE, and in-phase T1W-GRE sequences. The SIR and CNR at precontrast were highest for EP imaging, and those at postcontrast were highest for T2*W-GRE. CONCLUSION: SHU-555-A will increase the detectability of HCC and its liver metastases. T1W- and T2*W-GRE sequences would be the sequences of choice.

Dynamic 99Tcm-ECD SPET correlates well with 201Tl indices in brain tumours.

The dynamic 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) single photon emission tomographic (SPET) characteristics of brain tumours were investigated and compared with 201Tl-chloride SPET indices. Thirty-five patients with histologically confirmed benign and malignant tumours were evaluated using dynamic and standard 99Tcm-ECD. Twenty-eight patients were also examined using standard 201Tl SPET. The following 201Tl indices were calculated: early uptake ratio, delayed uptake ratio, washout rate and retention index. The relationship between uptake of 99Tcm-ECD on dynamic SPET and 201Tl indices was analysed. Nine patients showed positive uptake on dynamic 99Tcm-ECD SPET, all of whom had benign tumours, including five meningothelial meningiomas, three pituitary adenomas of the chromophobe type and one chemodectoma without malignancy. The mean early uptake ratio of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (17.1 +/- 5.5 vs 9.0 +/- 5.7, P = 0.004). The mean washout rate of the tumours with positive uptake was significantly higher than that of the tumours with negative uptake (61.0 +/- 27.7 vs 0.35 +/- 30.9, P = 0.0004). The mean retention index of the tumours with positive uptake was significantly lower than that of the tumours with negative uptake (0.27 +/- 0.12 vs 0.88 +/- 0.48, P = 0.000006). Only benign tumours showed positive uptake on dynamic 99Tcm-ECD SPET. The 201Tl indices correlated well with the uptake of 99Tcm-ECD on dynamic SPET. The results suggest that dynamic 99Tcm-ECD SPET can identify the benign character of tumours of the brain.

Dynamic SPET parameters of 123I-MIBG cardiac imaging.

Early dynamic and late 123I-MIBG SPET studies were performed to investigate several parameters used to distinguish the characteristics of various cardiac disorders. Forty-six individuals (34 non-diabetic, 12 diabetic) with or without heart disease were included in the study. Early dynamic and late static SPET images were acquired using a triple-headed gamma camera. After selecting mid-sections from vertical (VLA) and horizontal (HLA) long-axis images, regions of interest were created over the apex, whole heart and anterior, inferior, septal and lateral walls of the heart. Various uptake ratios at 3, 11 and 19 min and 4 h after injection (HU3, HU11, HU19, DUP) and clearances (Kse: between HU3 and HU11; Ke: between HU11 and HU19; Kd: between HU19 and DUP) were calculated. There were significant differences among various cardiac pathologies on the delayed images. Cardiomyopathy patients showed the lowest uptake on the delayed images. When all segments in normal patients and all involved segments in myocardial infarcted patients were compared, there was significantly lower uptake of MIBG in infarcted segments at all time points. Kd showed the lowest value compared with Kse and Ke. In cardiomyopathy patients, Kse, Ke and Kd were significantly different from each other. Both Kse and Ke were significantly higher in cardiomyopathy patients than in normal patients. In conclusion, the results of this study are in line with published data and precise measurement of uptake and clearance was possible when excluding background and blood pool activity.

Perfusion MR imaging with a superparamagnetic iron oxide using T2-weighted and susceptibility-sensitive echoplanar sequences: evaluation of tumor vascularity in hepatocellular carcinoma.

OBJECTIVE: The study purpose was to examine the usefulness of perfusion echoplanar MR imaging with a superparamagnetic iron oxide (SHU-555A) for evaluating the vascularity of hepatocellular carcinomas. SUBJECTS AND METHODS: Twenty-two patients with 32 hepatocellular carcinomas underwent perfusion imaging with bolus injection (0.7-1.1 ml) of SHU-555A. Echoplanar sequences included multishot spin-echo (17 patients) and single-shot gradient-echo (five patients) imaging. Image acquisition was repeated every 30 sec for 3 min with the multishot spin-echo sequence and every 2 sec for 100 sec with the single-shot gradient-echo sequence. Lesion signal intensity versus time curves were created for quantitative analysis. RESULTS: Transient decreases in tumor signal intensity (28.8% with multishot spin-echo and 63.3% with the single-shot gradient-echo) were seen in the perfusion phase. These decreases in signal intensity were statistically significantly (p < .01) different for each histologic type of hepatocellular carcinoma (poorly differentiated, 43.3%; well differentiated, 18.4%; and moderately differentiated, 24.8%). After the perfusion phase, the tumor signal intensities rapidly recovered. The multishot spin-echo sequence could detect some signal changes even in lesions smaller than 1 cm. CONCLUSION: Hepatocellular carcinoma vascularity can be evaluated with perfusion echoplanar imaging with SHU-555A. Because of its excellent temporal resolution, the single-shot gradient-echo echoplanar sequence detects the transient signal decrease in most lesions. The high image quality of the multishot spin-echo echoplanar sequence allows evaluation of the vascularity of even very small lesions.

Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI.

Possible involvement of cell membrane ion transport systems in the uptake and extrusion of Tc-99m-MIBI was investigated by using various buffers with or without Na+ and Ca++, and ion transport inhibitors in a tumor cell line. The ion transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all buffers containing either Na+ or Ca++ alone or none of them. There was significantly increased uptake of Tc-99m-MIBI especially in buffers without Na+. Verapamil, a L-type Ca++ channel blocker, increased Tc-99m-MIBI uptake in all buffers. Flunarizine, which inhibits Na+/ Ca++ channels, caused significantly increased accumulation of Tc-99m-MIBI only in buffer containing both Na+ and Ca++. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m-MIBI. DMA, a potent Na+/H+ antiport inhibitor, significantly inhibited the uptake of Tc-99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na+ during its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil- and flunarizine-sensitive pathways.

Detection of lung lesions and lymph nodes with 201Tl SPET.

The aim of this study was to characterize lung lesions by means of the uptake, retention and washout of 201Tl, and to quantify the sensitivity of 201Tl SPET (single photon emission tomography) in detecting mediastinal and hilar lymph nodes. A total of 68 patients with lung lesions (tumours and inflammation) underwent both helical computed tomography (CT) and 201Tl SPET examinations. Uptake, retention and washout parameters were calculated from early and delayed 201Tl SPET by drawing regions of interest over the primary lesion and the background of the lung. The findings on 201Tl SPET were compared with those on CT and surgical findings. A significant difference in the retention index (RI) was observed between primary malignant and benign lesions. In detecting lymph nodes, the sensitivity, specificity and negative predictive value were 83%, 60% and 90% respectively for early 201Tl SPET, and 50%, 80% and 80% respectively for delayed 201Tl SPET. 201Tl SPET with semi-quantitative analysis, especially RI, helps to differentiate between malignant and benign lung lesions. Lymph nodes larger than 1 cm on CT but not showing 201Tl uptake could be considered non-metastatic lesions.

Detection of lung and chest tumours using 99Tcm-tetrofosmin: comparison with 201Tl.

The aim of this study was to assess the usefulness of 99Tcm-tetrofosmin for detecting tumours of the lungs and adjacent structures and to compare the results with those for 201Tl. In the 18 patients studied, there were 30 lesions in total. Dual-isotope SPET acquisitions were performed 10 min and 3 h after the administration of 99Tcm-tetrofosmin and 201Tl. Image quality and semi-quantitative parameters were evaluated for both tracers. All lesions were detected by the two radiopharmaceuticals on both the early and delayed images. In seven patients, the image quality of 99Tcm-tetrofosmin was better than that of 201Tl. For the detection of metastatic lymph nodes, the delayed 201Tl and the early 99Tcm-tetrofosmin images were superior. No significant difference was observed between the uptake ratios of the two tracers. 99Tcm-tetrofosmin showed significantly (P < 0.001) higher washout than 201Tl from both the lesions and normal lungs, although washout of 201Tl from normal lungs was significantly higher than that from the lesions. In conclusion, 99Tcm-tetrofosmin may be helpful for detecting tumours of the lungs and adjacent structures, but has limited applicability in differentiating between malignant and benign tumours and may not be used instead of 201Tl to detect malignant tumours of the lungs.

Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells.

UNLABELLED: The mechanisms of uptake and intracellular distribution of 99mTc-tetrofosmin, 99mTc-MIBI and 201TI and the behaviors of 99mTc-tetrofosmin and 99mTc-MIBI in relation to Na+ were studied with primary cultures of myocardial cells. METHODS: Both the uptake and the washout of the tracers were sequentially measured. The cells were treated with ouabain, bumetanide, tetrodotoxin, dimethyl amiloride (DMA), nigericin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) to observe the effects of the uptake and intracellular distribution of the traders. Cells equilibrated in buffers with or without Na+ were treated with monensin and DMA to evaluate the effect of Na+ on the accumulation of the tracers. RESULTS: Despite the similarities in uptake kinetics, there was a higher level of retention of 99mTc-tetrofosmin inside the cells. Ouabain, bumetanide and tetrodotoxin did not show any inhibitory effect on the uptake of 99mTc-tetrofosmin and 99mTc-MIBI, whereas they produced various degrees of inhibition of 201TI uptake. DMA produced approximately 35% inhibition of 99mTc-tetrofosmin uptake and 50% inhibition of 99mTc-MIBI uptake. Nigericin increased the uptake of 99mTc-MIBI by the cells. The addition of CCCP produced the release of 38% of the accumulated 99mTc-tetrofosmin and 52%-70% of the accumulated 99mTc-MIBI, indicating that these percentages of accumulation were related to mitochondrial uptake. Neither Na+-free buffer nor monensin had any significant effect on 99mTc-tetrofosmin accumulation, but they both caused increased accumulation of 99mTc-MIBI. CONCLUSION: The uptake of both 99mTc-tetrofosmin and 99mTc-MIBI through the cell membrane is partly related to the Na+/H+ antiporter system. Only part of the accumulated 99mTc-tetrofosmin inside the cells enters into mitochondria; most of the accumulated 99mc-MIBI is related to mitochondrial uptake. This uptake may be related to Na+.