Enhanced washout of <Superscript>99m</Superscript>Tc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional <Superscript>123</Superscript>I-BMIPP uptake and wall thickness determined by MRI

Ohne Zusammenfassung     

Reduction of <Superscript>99m</Superscript>Tc-sestamibi and <Superscript>99m</Superscript>Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of ^99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, ^99mTc-tetrofosmin (TF), was also examined. Cellular uptake of ^99mTc-MIBI and ^99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N₂ and 5% CO₂ reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.     

Use of quantitative SPECT/CT reconstruction in <Superscript>99m</Superscript>Tc-sestamibi imaging of patients with renal masses

Objective

Technetium-99m (^99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with ^99mTc-sestamibi.

Methods

Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions.

Results

The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions.

Conclusions

Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal ^99mTc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions.

     

Myocardial washout of <Superscript>99m</Superscript>Tc-tetrofosmin and response to steroid therapy in patients with cardiac sarcoidosis

Objective  

Early diagnosis and initiating treatment of cardiac sarcoidosis are essential because cardiac involvement is an important prognostic factor. Although there are many reports on the diagnosis of cardiac sarcoidosis, the literature on predicting the efficacy of steroid therapy is very limited. The purposes of this study were to investigate the myocardial washout of ^99mTc-tetrofosmin (TF), and to evaluate the predictability of left ventricular (LV) functional recovery after steroid therapy in patients with cardiac sarcoidosis.     

Brown adipose tissue: Evaluation with<Superscript>201</Superscript>Tl and<Superscript>99m</Superscript>Tc-sestamibi dual-tracer SPECT

Brown adipose tissue is one kind of adipose tissue and regulates body temperature and balance of energy via non-shivering thermogenesis. The authors present a case that strongly suggested the presence of activated brown adipose tissue in the neck, shoulders and axillary space by increased 18F-FDG uptake. 99mTc-sestamibi and 201Tl dual-tracer SPECT study showed increased 99mTc-sestamibi uptake and non-increased 201Tl uptake in the corresponding 18F-FDG uptake sites. Brown adipose tissue has dense mitochondria in the cells, which play an important role in thermogenesis. 99mTc-sestamibi uptake and retention depend on the mitochondrial activity but 201Tl uptake does not. Therefore, the activity of mitochondria in activated brown adipose tissue may explain the discrepant uptake between 99mTc-sestamibi and 201Tl.     

Interpretation of reverse redistribution of <Superscript>99m</Superscript>Tc-tetrofosmin in patients with acute myocardial infarction

Reverse redistribution (RR) of technetium-99m tetrofosmin (TF) in patients with acute myocardial infarction (AMI) has been considered a sign of salvaged myocardium. We examined the time evolution of the RR pattern during a 6-month period and the clinical implications of RR. TF myocardial SPET was performed in 22 patients 1 week, 1 month and 3-6 months after AMI. Myocardial images were obtained 30 min and 180 min after the injection of TF. Regional uptake of TF was rated using a four-point scoring system. RR was defined as an increase of more than 1 point in the regional score on images obtained at 180 min. Echocardiography was performed to assess regional wall motion at the same time as TF imaging. RR observed at 1 week tended to disappear after 1 month and 3-6 months. The incidence of regional wall motion abnormality was reduced in patients with RR compared with that in patients with fixed defects. Recovery of abnormal regional wall motion occurred earlier in segments with disappearance of RR than in those without disappearance of RR. It is concluded that RR may reflect salvaged myocardium and that disappearance of RR may indicate earlier recovery of salvaged myocardium.     

Left ventricular function in response to dipyridamole stress: head-to-head comparison between <Superscript>82</Superscript>Rubidium PET and <Superscript>99m</Superscript>Tc-sestamibi SPECT ECG-gated myocardial perfusion imaging

Purpose

Myocardial perfusion imaging (MPI) with ^99mTc-sestamibi (sestamibi) SPECT and rubidium-82 (⁸²Rb) PET both allow for combined assessment of perfusion and left ventricular (LV) function. We sought to compare parameters of LV function obtained with both methods using a single dipyridamole stress dose.

Materials and methods

A group of 221 consecutive patients (65.2?±?10.4 years, 52.9% male) underwent consecutive sestamibi and ⁸²Rb MPI after a single dipyridamole stress dose. Sestamibi and ⁸²Rb summed rest (SRS), stress (SSS) and difference (SDS) scores, and LV end-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were compared.

Results

Bland-Altman analysis showed that with increasing ESV and EDV the difference between the two perfusion tracers increased both at rest and post-stress. The mean difference in EDV and ESV between the two perfusion tracers at rest could both be independently explained by the ⁸²Rb SDS and the sestamibi SRS. The combined models explained approximately 30% of the variation in these volumes between the two perfusion tracers (R²?=?0.261, p?=?0.005; R²?=?0.296, p?<?0.001, for EDV and ESV respectively). However, the mean difference in LVEF between sestamibi and ⁸²Rb showed no significant trend post-stress (R²?=?0.001, p?=?0.70) and only a modest linear increase with increasing LVEF values at rest (R²?=?0.032, p?=?0.009).

Conclusions

Differences in left ventricular volumes between sestamibi and ⁸²Rb MPI increase with increasing volumes. However, these differences did only marginally affect LVEF between sestamibi and ⁸²Rb. In clinical practice these results should be taken into account when comparing functional derived parameters between sestamibi and ⁸²Rb MPI.

     

<Superscript>99m</Superscript>Tc-HMPAO and <Superscript>99m</Superscript>Tc-ECD perform differently in typically hypoperfused areas in Alzheimer's disease

Ohne Zusammenfassung     

Abnormal retention of<Superscript>99m</Superscript>Tc-TF in a hamster model of cardiomyopathy analyzed by<Superscript>99m</Superscript>Tc-TF and<Superscript>125</Superscript>I-BMIPP autoradiography

OBJECTIVE: Enhanced washout of 99mTc-tetrofosmin (TF) has been reported in patients with hypertrophic cardiomyopathy (HCM). Here, using quantitative dual-autoradiography, the relationship between TF retention abnormality and metabolism depicted by 125I-BMIPP uptake was investigated quantitatively in a hamster model of cardiomyopathy. METHODS AND RESULTS: Early and delayed TF images were obtained at 5 min (7 cardiomyopathic and 5 normal hamsters) and 60 min (8 cardiomyopathic and 5 normal hamsters) after injection, respectively. BMIPP image was obtained 5 min after injection. Five cardiomyopathic and 5 normal hamsters were evaluated histologically. Percent uptake of TF and BMIPP in the heart was measured by an auto-well counter. The left ventricular wall was divided into 12 segments, and the relative regional uptake of TF and BMIPP was measured for each segment. Heterogeneity of radioactive distribution was determined by the standard deviation (SD) of radioactive counts in the left ventricular wall on autoradiogram. The uptake of early TF, delayed TF, and BMIPP in cardiomyopathic hamsters was 8.8%, 20.3%, and 25.3% lower than that in normal hamsters, p < 0.05, p < 0.01, and p < 0.001, respectively. In normal hamsters, distribution of radioactivity in all images was homogeneous, and the SD values were about 13. In cardiomyopathic hamsters, heterogeneous distribution was observed on all images, and the degree of heterogeneity was marked on delayed TF and BMIPP images. The SD was 19.7 +/- 1.2 for early TF image, 25.5 +/- 1.4 for delayed TF image, and 31.7 +/- 2.4 for BMIPP image, respectively. A weak linear correlation was observed between the relative regional uptake of the delayed TF and BMIPP in cardiomyopathic hamsters (r = 0.57). Electron microscopy demonstrated ultra-structural changes in mitochondria of cardiomyopathic hamsters. CONCLUSION: Degree of retention abnormality on delayed TF image corresponded to the metabolic abnormality, probably due to mitochondrial dysfunction, depicted on BMIPP imaging.     

Questionnaire survey of hospitals in Saitama Prefecture regarding the shortage of <Superscript>99m</Superscript>Tc-labeled radiopharmaceuticals and <Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators

Objective and methods  

A questionnaire survey was conducted at all 32 hospitals in Saitama Prefecture to investigate the current difficult situation in terms of nuclear medicine management in the face of the ^99mTc shortage due to insufficient supply, and 29 hospitals (90.6%) replied.     

Estimation of myocardial blood flow and myocardial flow reserve by <Superscript>99m</Superscript>Tc-sestamibi imaging: comparison with the results of [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O PET

We developed a noninvasive method to quantitatively estimate the myocardial blood flow (MBF) index and flow reserve (MFR) using dynamic and static data obtained with technetium-99m sestamibi, and compared the results with MBF and MFR measured by oxygen-15-labeled water ([(15)O]H(2)O) PET. Twenty patients with coronary artery disease (CAD) and nine normal subjects underwent both (99m)Tc-sestamibi and PET studies within 2 weeks. From the anterior view, dynamic data were acquired for 2 min immediately after the injection of (99m)Tc-sestamibi, and planar static images were also obtained after 5 min at rest and during ATP stress (0.16 mg kg(-1) min(-1) for 5 min) on another day. The area under the time-activity curve on the aortic arch (Aorta ACU), myocardial weight with the SPET image (M), and the myocardial count on the planar image for 1 min (C(m)) were obtained. The MBF index (MBFI) was calculated as follows: MBFI=Cm/Aorta ACU x 100M. MFR was measured by dividing the MBFI at ATP stress by MBFI at rest. The MBFI measured by (99m)Tc-sestamibi was significantly correlated with MBF obtained using [(15)O]H(2)O PET (MBFI=13.174+11.732 x MBF, r=0.821, P<0.001). Furthermore, MFR measured by (99m)Tc-sestamibi was well correlated with that obtained using [(15)O]H(2)O PET, with some underestimation (r=0.845, P<0.001). MFR using (99m)Tc-sestamibi in patients with CAD was significantly lower than that in normal subjects (CAD: 1.484+/-0.256 vs normal: 2.127+/-0.308, P<0.001). These data suggest that the MBFI and MFR can be measured with (99m)Tc-sestamibi. This may be useful for the quantitative assessment of CAD, especially in those patients with diffuse coronary disease.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

Single-photon agents for tumor imaging:<Superscript>201</Superscript>TI,<Superscript>99m</Superscript>Tc-MIBI,and<Superscript>99m</Superscript>Tc-tetrofosmin

This review aims at fostering comprehension and knowledge not only for expert physicians who can skillfully handle various techniques for tumor imaging but also for young practitioners in the field of nuclear medicine. As image processing software and hardware become smaller, faster and better, SPECT will adapt and incorporate these advances. A principal advantage of SPECT over PET is the more widespread availability of the equipment and lower cost for the introduction of the system in community-based facilities. Moreover, SPECT has become less dependent on a limited number of acknowledged experts for its interpretation owing to a variety of handy computer tools for imaging analyses. The increasing use of PET in tumor imaging is not necessarily proportional to the decline of SPECT. General physicians' attention to SPECT technology would also increase more by evoking their interest in "tracer imaging."     

Effect of attenuation correction on the interpretation of <Superscript>99m</Superscript>Tc-sestamibi myocardial perfusion scintigraphy: the impact of 1 year's experience

The aim of this study was to determine the yield of attenuation correction in myocardial perfusion imaging (MPI), before and after a 1-year experience period. In 48 consecutive patients referred for MPI, both non-corrected (NC) and attenuation-corrected (AC) images were analysed by three independent readers shortly after implementation of attenuation correction. The same images were re-analysed 1 year later, after having obtained experience in attenuation correction on a routine basis in >500 patients with clinical feedback. Results were compared with gold standards for ischaemia and infarction based on coronary angiography, follow-up, ultrasound and gated blood pool imaging. Sensitivity and specificity for the detection of coronary artery disease were 95% and 45% respectively for NC images and 77% and 70% respectively for AC images at first readings. After 1 year of AC experience, NC sensitivity/specificity was 100%/61%, and AC results were 89%/92%. It is concluded that attenuation correction improves the performance of MPI interpretation. With attenuation correction, specificity is increased and sensitivity is similar as compared with NC images. However, attenuation correction requires experience and is associated with a learning curve.     

<Superscript>99m</Superscript>Tc-depreotide scintigraphy of bone lesions in patients with lung cancer

Purpose Scintigraphy with ^99mTc-depreotide, a somatostatin analogue–technetium ligand, has been used for evaluation of various malignant neoplasms, including lung cancer. The diagnosis of bone metastases in patients with lung cancer is not always definitive with current imaging methods. Visualisation of somatostatin receptors (SSTRs) in bone lesions, when the primary tumour exhibits such receptors, could be helpful in characterising them as metastatic. The aim of this study was to assess the value of ^99mTc-depreotide in differentiating between benign and malignant bone lesions in patients with lung cancer.Methods The study population comprised 20 patients (17 males and three females, mean age 63 years) with proven lung cancer in whom bone lesions had been detected by conventional imaging methods. All patients underwent ^99mTc-hydroxydiethylene diphosphonate and ^99mTc-depreotide scintigraphy within 2 weeks. Bone lesions were classified as benign or malignant on the basis of clinical, imaging and/or histological criteria.Results ^99mTc-depreotide uptake in the primary tumour was seen in 19 of the 20 patients. Conventional imaging methods detected 55 bone lesions, 31 of which were classified as malignant. Twenty-eight (90%) of these lesions showed ^99mTc-depreotide uptake, suggesting bone metastases, while three did not. Twenty-four bone lesions were classified as benign by conventional imaging methods, and none of them showed ^99mTc-depreotide uptake. In addition, ^99mTc-depreotide demonstrated extra-osseous lesions in six patients.Conclusion In patients with lung cancer and bone lesions, ^99mTc-depreotide scintigraphy uptake in the bone lesions supports the diagnosis of malignancy, in particular if the primary lung tumour also exhibits SSTRs. Furthermore, whole-body ^99mTc-depreotide scintigraphy may disclose extra-osseous disease.     

Regional differences between <Superscript>99m</Superscript>Tc-ECD and <Superscript>99m</Superscript>Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether ^99mTc-HMPAO or ^99mTc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8±6.6 years) were assigned to ^99mTc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6±6.7 years) to ^99mTc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq ^99mTc-HMPAO or ^99mTc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether ^99mTc-HMPAO and ^99mTc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.