Myocardial perfusion SPECT as a potential mediator on circulating chromogranin A in patients with old myocardial infarction.

OBJECTIVE: Chromogranin A (CgA) is a soluble polypeptide stored within and released from secretory granules of endocrine and other cell types (including cardiomyocytes); CgA appears to be a marker of the overall neuroendocrine activity. Increased levels of serum CgA have been found not only in patients with neuroendocrine neoplasms but also with other malignancies, hypertension, myocardial infarction, heart, or renal failure. SUBJECTS AND METHODS: A population of 307 patients (202 males, 105 females) was enrolled. The study group consisted of 118 individuals (38.4%) with myocardial infarction more than one year old (MI group); the remaining 189 (61.6%) had no known heart disease (control group). All patients underwent myocardial perfusion scintigraphy (MPS) after blood withdrawal for serum CgA measurement. To test whether a possible effect of old infarction on serum CgA is mediated by MPS findings, we employed analysis of covariance for three distinct categories of left ventricular (LV) perfusion deficits as dichotomous predictors: (1) any-type deficits (abnormal MPS); (2) reversible deficits (ischemia); and (3) fixed deficits (scar). RESULTS: In all three MPS conditions, the effect of age, gender, and LV ejection fraction (EFLV) on serum CgA was statistically significant: women exhibited higher CgA levels than men (P=0.008-0.023), whereas increasing age and decreasing EFLV were associated with increasing CgA (all P<0.001). Conversely, no statistically significant differences in mean CgA levels were found between MI patients and normal controls with either abnormal MPS, scar, or ischemia, or their degree and extent. CONCLUSION: Although serum CgA is significantly associated with age, gender, and EFLV in patients with an old MI, no association was found between CgA levels and either old MI history or MPS findings. The verified involvement of circulating CgA in the acute/subacute phase of infarction appears to be blunted in infarctions older than a year.

Is there still a place for SPET in the era of PET brain imaging?

Although positron emission tomography (PET) may be credited with providing the impetus for the new clinical interest in functional neuroimaging and currently is an increasingly important imaging tool for noninvasive assessment of brain tumors, single-photon emission tomography (SPET) has offered an alternative technique with the relative advantages of lower price and wide availability. Brain SPET has been proven useful in the differentiation of tumor recurrence from radiation necrosis, in the non-invasive assessment of gliomas and meningiomas aggressiveness, in differentiating neoplastic from non neoplastic intracerebral haemorrhage, in monitoring treatment response and estimating patients' prognosis. Thus, SPET may still have a role in the diagnosis and characterization of brain tumors. Future comparative studies between SPET and PET or latest magnetic resonance based neuroimaging techniques are warranted.

Characterization of intracranial space-occupying lesions by 99(m)Tc-Tetrofosmin SPECT.

Differentiating neoplastic from non-neoplastic intracranial lesions is of paramount importance for patient management. Benign lesions can have many of the features of malignant brain tumors on both computed tomography (CT) and conventional magnetic resonance imaging (MRI). Herewith, we set out to investigate the role of (99m)Tc-Tetrofosmin (99(m)Tc-TF) brain SPECT in the differentiation of neoplastic from non-neoplastic intracranial lesions. We prospectively studied, between September 2004 and September 2009, patients with intracranial lesions suspected of being tumors on CT/MRI that were operated on. All patients with suspected tumor on CT/MRI underwent 99(m)Tc-TF brain SPECT within a week before surgery and CT/MRI studies. Radiotracer accumulation in intracranial lesions was assessed visually and then a semiquantitative method of image analysis was applied, by calculating the lesion-to-normal (L/N) uptake ratio. We compared the L/N ratios between low-grade gliomas and high-grade gliomas, low and high-grade gliomas and intra-axial non-neoplastic lesions, low and high-grade gliomas and metastases, and typical versus anaplastic meningiomas Ninety patients suffered from neoplastic lesions and 16 harboured non-neoplastic pathologies. There was a significant difference between low-grade gliomas and high-grade gliomas (P = 0.0019). ROC analysis provided 2.8 as the optimum cutoff value thresholding discrimination between these two groups, with 91.3% sensitivity and 83.3% specificity. When comparing gliomas (low and high-grade) with intra axial non-neoplastic lesions the difference was statistically significant (P < 0.0001). There was no statistically significant difference between gliomas (low and high-grade) and metastases. Regarding meningiomas, there was a statistically significant difference between typical and anaplastic meningiomas (P = 0.0002). ROC analysis provided 9.6 as the optimum cutoff value thresholding discrimination between these two groups, with 96% sensitivity and 100% specificity. (99m)Tc-TF brain SPECT may differentiate neoplastic from non-neoplastic intracranial pathologies and could prove useful for pre-surgical evaluation of intracranial lesions.

Glioma recurrence versus radiation necrosis: accuracy of current imaging modalities.

Treatment for brain gliomas is a combined approach of surgery, radiation therapy and chemotherapy. Nevertheless, high-grade gliomas usually recur despite treatment. Ionizing radiation therapy to the central nervous system may cause post-radiation damage. Differentiation between post-irradiation necrosis and recurrent glioma on the basis of clinical signs and symptomatology has not been possible. Computed tomography (CT) and magnetic resonance imaging (MRI) suffer from significant limitations when applied to differentiate recurrent brain tumor from radiation necrosis. We reviewed the contribution of recent MRI techniques, single-photon emission CT and positron emission tomography to discriminate necrosis for glioma recurrence. We concluded that despite the progress being made, further research is needed to establish reliable imaging modalities that distinguish between true tumour progression and treatment-related necrosis.

Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis.

PURPOSE: Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. METHODS: We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), C-methionine (MET), and F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas. RESULTS: Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. CONCLUSIONS: This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade.

Evaluation of meningioma aggressiveness by (99m)Tc-Tetrofosmin SPECT.

OBJECTIVES: Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase -- as determined by DNA flow cytometry -- are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. PATIENTS AND METHODS: Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by (99m)Tc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. RESULTS: Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r=0.733, P=0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. CONCLUSION: These results imply that (99m)Tc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity.

Rapidly progressing glioblastoma resembling brain abscess in leukemia.

A 63-year-old man with a history of chronic lymphocytic leukemia and a prosthetic aortic valve was hospitalized because of a mastoiditis, complicated by meningitis and epileptic seizures. Two weeks later he developed a lesion in the right temporal lobe. A brain abscess was suspected. However after treatment his clinical condition failed to improve. 99mTc-Tetrofosmin brain SPECT was performed and revealed substantially increased tracer uptake. Due to the patient's clinical deterioration, surgery was considered most appropriate. Histopathology established the diagnosis of glioblastoma multiforme. This case suggests a note of caution in every case of a rapidly evolving space-occupying lesion independently of the patient's previous history.

Brain scintigraphy with 99mTc-tetrofosmin for the differential diagnosis of a posterior fossa tumor.

A 60-year-old woman harbouring a tumour in the cerebellum. Anatomic brain imaging by computed tomography and magnetic resonance imaging were not conclusive of the lesion's nature. Imaging by (99m)Tc-tetrofosmin single-photon emission tomography (SPET) showed increased radiotracer accumulation in the lesion, indicating a vascular supply, membrane permeability and cellular metabolic activity, which is suggested to facilitate tracer uptake by lesions located in the posterior fossa. The patient underwent surgery and haemangioblastoma was confirmed by histology. Differential diagnosis is discussed. (99m)Tc-tetrofosmin scintiscan contributed to diagnostic information.

Osteomyelitis: antigranulocyte scintigraphy with 99mTC radiolabeled monoclonal antibodies for diagnosis-- meta-analysis.

PURPOSE: To perform a meta-analysis of the sensitivity and specificity of antigranulocyte scintigraphy with monoclonal antibodies (MoAbs) in the diagnosis of osteomyelitis across different patient groups and clinical settings. MATERIALS AND METHODS: MEDLINE and EMBASE searches were conducted. Data on the diagnostic performance of antigranulocyte scintigraphy with MoAbs were combined. Weighted sensitivities and specificities were estimated by using a random-effects model that incorporated between-study heterogeneity and by constructing summary receiver operating characteristic (ROC) curves. The weighted positive and negative likelihood ratios (LRs) across studies were estimated. Data syntheses were performed for all patients and for various subgroups. The reference standard used in each individual study was accepted. RESULTS: Nineteen nonoverlapping studies with a total of 714 examinations and reference standards of cell culture, histologic examination, clinical follow-up, and radiologic examination were eligible. The independent random-effects summary estimates of sensitivity and specificity were 81% (95% confidence interval [CI]: 70%, 88%) and 77% (95% CI: 66%, 86%), respectively, with statistically significant between-study heterogeneity (exact P < .001 for both metrics). In the summary ROC curve, a sensitivity of 81% corresponded to a specificity of 86%, and a specificity of 77% corresponded to a sensitivity of 87%. The weighted positive LR was 3.02 (95% CI: 2.07, 4.42), and the weighted negative LR was 0.26 (95% CI: 0.17, 0.39), with statistically significant between-study heterogeneity (exact P < .001 for both metrics). Sensitivity was better for peripheral than for axial skeleton lesions (87% vs 53%). CONCLUSION: Antigranulocyte scintigraphy with MoAbs has a sensitivity of 81% and a specificity of 77% in the diagnosis of osteomyelitis.

Olfactory colloid cyst.

Colloid cysts are rare intracerebral lesions that are predominantly located in the third ventricle. Extraventricular colloid cysts have only rarely been reported but so far there are no reports of a colloid cyst residing in the olfactory groove. A 74-year-old patient underwent a brain computed tomography scan for a mild head trauma that incidentally revealed a space-occupying lesion near the olfactory groove. Brain magnetic resonance imaging that ensued demonstrated a hyperintense lesion in T1, T2, and FLAIR sequences, without evidence of surrounding brain edema. To evaluate the metabolic status of the lesion, brain single-photon emission computed tomography with 99mTc-Tetrofosmin was then performed, revealing no tracer uptake, a finding consistent with benignity. Due to the diagnostic uncertainty the excision of the lesion was proposed. The patient underwent surgery and intraoperative a cyst was revealed. Furthermore the cyst seemed to erode the dura and due to its location there was an imminent danger for cerebrospinal fluid leak. Therefore a repair of the dura was performed and the cyst was excised totally. Histology verified the presence of a colloid cyst. Colloid cysts should be included in the differential diagnosis of lesions in the anterior fossa and although benign they may have an aggressive presentation by eroding the dura and producing CSF leak.

Evaluation of brain tumor recurrence by (99m)Tc-tetrofosmin SPECT: a prospective pilot study.

OBJECTIVE: The differentiation between brain tumor recurrence and post-irradiation injury remains an imaging challenge. Computed tomography (CT) and magnetic resonance imaging (MRI) cannot always distinguish between the two. Although glioma cell line studies substantiated a plausible imaging superiority of (99m)Tc-tetrofosmin ((99m)Tc-TF) over other radiopharmaceuticals, little has been reported on its in vivo imaging properties. We assessed (99m)Tc-TF single-photon emission CT (SPECT) in cases where morphologic brain imaging was inconclusive between recurrence and radionecrosis. METHODS: A total of 11 patients (7 men, 4 women) were evaluated. The initial diagnosis was glioblastoma multiforme (4), anaplastic astrocytoma (1), anaplastic oligodendroglioma (3), grade-II astrocytoma (2), and low-grade oligodendroglioma (1). All patients had been operated on and then received adjuvant external-beam radiotherapy. After a mean follow-up period of 25 months, there was clinical suspicion of recurrence, for which (99m)Tc-TF SPECT was performed. RESULTS: In 8/11 cases, an abnormally increased tracer uptake appeared in the region that CT and/or MRI indicated as suspicious; in half of these cases, recurrence was confirmed histologically after surgery and in the other four by growth of the lesion over a 6-month follow-up period, and clinical deterioration. The remaining 3/11 patients had faint tracer uptake in the suspicious region, compatible with radiation injury; these lesions remained morphologically unaltered in a mean 12-month follow-up period, with no clinical deterioration in the patient's condition, a course strongly favoring the diagnosis of radiation injury. CONCLUSIONS: Metabolic brain imaging by (99m)Tc-TF could offer useful information in the workup of treated brain tumors, where radiomorphologic findings between recurrence and radionecrosis are inconclusive.

99mTc-Tetrofosmin Uptake Correlates with the Sensitivity of Glioblastoma Cell Lines to Temozolomide.

99mTc-tetrofosmin (99mTc-TF) is a single-photon emission computed tomography tracer that has been used for brain tumor imaging. The aim of the study was to assess if 99mTc-TF uptake by glioblastoma cells correlates with their response to temozolomide (TMZ). We investigated the correlation of TMZ antitumor effect with the 99mTc-TF uptake in two glioblastoma cell lines. The U251MG cell line is sensitive to TMZ, whereas T98G is resistant. Viability and proliferation of the cells were examined by trypan blue exclusion assay and xCELLigence system. Cell cycle was analyzed with flow cytometry. The radioactivity in the cellular lysate was measured with a gamma scintillation counter. TMZ induced G2/M cell cycle arrest in U251MG cells, whereas there was no effect on cell cycle in T98G cells. Lower 99mTc-TF uptake was observed in U251MG cells that were exposed to TMZ compared to control (P = 0.0159). No significant difference in respect to 99mTc-TF uptake was found in T98G cells when exposed to TMZ compared to control (P = 0.8). With 99mTc-TF, it was possible to distinguish between TMZ-sensitive and resistant glioblastoma cells within 6 h of treatment initiation. Thus, 99mTc-TF uptake may consist a novel approach to assess an early response of glioblastoma to chemotherapy and deserves further investigation.

18F-FDG PET for evaluation of bone marrow infiltration in staging of lymphoma: a meta-analysis.

UNLABELLED: The ability of PET with (18)F-FDG to evaluate bone marrow infiltration in patients with lymphoma has been a matter of extensive investigation with controversial results. Therefore, we aimed to evaluate systematically, with a meta-analysis, the diagnostic performance of (18)F-FDG PET in this setting. METHODS: Relevant studies were identified with MEDLINE and EMBASE searches (last update, August 2004). Data on the diagnostic performance of (18)F-FDG PET were combined quantitatively across eligible studies. We estimated weighted summary sensitivities and specificities, summary receiver-operating-characteristic (SROC) curves, and weighted summary likelihood ratios. We also conducted separate analyses according to various subgroups. Bone marrow biopsy (BMB) was used as the reference standard. RESULTS: Thirteen eligible nonoverlapping studies, which enrolled a total of 587 patients, were included in the meta-analysis. The independent random-effects weighted estimates of sensitivity and specificity against BMB were 51% (95% confidence interval [CI], 38%-64%) and 91% (95% CI, 85%-95%), respectively. Results were consistent in the SROC curve: a sensitivity of 51% corresponds to a specificity of 92%, whereas a specificity of 91% corresponds to a sensitivity of 55%. The weighted positive likelihood ratio (LR+) was 5.75 (95% CI, 348-9.48) and the negative likelihood ratio (LR-) was 0.67 (95% CI, 0.55-0.82). Six of 12 patients with positive (18)F-FDG PET and negative initial biopsy were found to have bone marrow involvement when biopsy was performed at the sites with positive imaging signals. Subgroup analyses showed better sensitivity in patients with Hodgkin's disease and in aggressive histologic types of non-Hodgkin's lymphoma than in patients with less aggressive histologic types and in studies using unilateral BMB compared with those using bilateral biopsy. CONCLUSION: This meta-analysis showed that (18)F-FDG PET has good, but not excellent, concordance with the results of BMB for the detection of bone marrow infiltration in the staging of patients with lymphoma. (18)F-FDG PET may complement the results of BMB and its performance may vary according to the type of lymphoma.

Comparison of (99m)tc-tetrofosmin and (99m)tc-sestamibi uptake in glioma cell lines: the role of p-glycoprotein expression.

(99m)Tc-Tetrofosmin ((99m)Tc-TF) and (99m)Tc-Sestamibi ((99m)Tc-MIBI) are SPECT tracers that have been used for brain tumor imaging. Tumor's multidrug resistance phenotype, namely, P-glycoprotein (p-gp), and the multidrug resistance related proteins (MRPs) expression have been suggested to influence both tracers' uptake. In the present study we set out to compare (99m)Tc-TF and (99m)Tc-MIBI uptake in high-grade glioma cell lines and to investigate the influence of gliomas p-gp expression on both tracers' uptake. We used four glioma cell lines (U251MG, A172, U87MG, and T98G). The expression of p-gp protein was evaluated by flow cytometry. Twenty µCi (7.4·10(5) Bq) of (99m)Tc-TF and (99m)Tc-MIBI were used. The radioactivity in the cellular lysate was measured with a dose calibrator. P-gp was significantly expressed only in the U251MG cell line (P < 0.001). In all gliomas cell lines (U251MG, U87MG, A172, and T98G) the (99m)Tc-TF uptake was significantly higher than (99m)Tc-sestamibi. The U251MG cell line, in which significant p-gp expression was documented, exhibited the strongest uptake difference. (99m)Tc-TF uptake was higher than (99m)Tc-MIBI in all studied high-grade glioma cell lines. Thus, (99m)Tc-TF may be superior to (99m)Tc-MIBI for glioma imaging in vivo.

Correlation of diffusion tensor, dynamic susceptibility contrast MRI and (99m)Tc-Tetrofosmin brain SPECT with tumour grade and Ki-67 immunohistochemistry in glioma.

OBJECTIVE: Assessment of the grade and type of glioma is of paramount importance for prognosis. Tumour proliferative potentials may provide additional information on the behaviour of the tumour, its response to treatment and prognosis. The purpose of this study was to investigate the correlation between diffusion tensor imaging (DTI), dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography (SPECT), and the tumour grade and Ki-67 labelling index in newly diagnosed gliomas. METHODS: Study was made of patients with suspected glioma on brain MRI between December 2010 and January 2012, by DTI, DSC MRI and (99m)Tc-Tetrofosmin brain SPECT. The proliferative activity of each tumour was measured by deriving the Ki-67 proliferation index from immunohistochemical staining of tumour specimens. RESULTS: Glioma was newly diagnosed in 25 patients (17 men, 8 women, aged 19-79 years, median 55 years). The Ki-67 index ranged from 1% to 80% (mean 19.4%). On evaluation of the relationship between the (99m)Tc-Tetrofosmin tumour uptake by gliomas was found to be significantly correlated with cellular proliferation (rho=0.924, p<0.0001). Regarding DTI, significant negative correlation was demonstrated between the apparent diffusion coefficient (ADC) ratio and the Ki-67 index (rho=-0.545, p=0.0087). Significant correlation was also observed between the fractional anisotropy (FA) ratio and the Ki-67 index (rho=0.489, p=0.02). Strong correlation was found between relative cerebral blood volume (rCBV) and Ki-67 index (rho=0.853, p<0.0001), and between the (99m)Tc-Tetrofosmin lesion-to-normal (L/N) uptake ratio and rCBV (rho=0.808, p ≤ 0.0001). Significant negative correlation was demonstrated between the (99m)Tc-Tetrofosmin L/N ratio and ADC ratio (rho=-0.513, p=0.014). These imaging techniques were able to distinguish between low-grade and high-grade gliomas. CONCLUSIONS: Findings on DSC MRI and brain SPECT with (99m)Tc-Tetrofosmin metrics were more closely correlated with glioma cellular proliferation.

Comparison of diffusion tensor, dynamic susceptibility contrast MRI and (99m)Tc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma.

INTRODUCTION: Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and (99m)Tc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis. METHODS: A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, (99m)Tc-Tetrofosmin brain SPECT. RESULTS: Both (99m)Tc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between (99m)Tc-Tetrofosmin uptake ratio and rCBV (P=0.003). CONCLUSIONS: Dynamic susceptibility contrast MRI and brain SPECT with (99m)Tc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.