Comparison of the uptake and clearance of Tc-99m MIBI, Tl-201 and Ga-67 in drug-resistant lymphoma cell lines.

Tc-99m sestamibi (MIBI) has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of Tc-99m MIBI in vincristine-resistant lymphoma cell lines. In addition, thallium-201 (Tl-201) and gallium-67 (Ga-67) uptake and clearance characteristics were evaluated for comparison with Tc-99m MIBI. Drug-resistant lymphoma cell lines (monocyte-like, histiocytic lymphoma, human; B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hodgkin's disease, lymphoid, human) were selected by multistep vincristine treatment up to 50 nM. After incubation of the radiotracers, Tc-99m MIBI, Tl-201 and Ga-67, in medium for 0, 10, 20, 30, 60 or 120 min, the uptake and clearance of each radiotracer were measured in the drug-resistant lymphoma cell lines. In addition, P-glycoprotein expression was determined by immunohistochemical study. In a comparison of the three radiotracers, the uptake of Tc-99m MIBI was the greatest in the studied wild-type lymphoma cell lines. Tc-99m MIBI uptake was much lower in drug-resistant tumor cell lines than in non-resistant cell lines. On the other hand, the uptake characteristics of Tl-201 did not differ between drug-resistant and non-resistant cells. Immunohistochemistry analyses of Ab-1 or JSB indicated that tumor cells expressed MDR-1 protein in all three cell lines. Tc-99m MIBI is a good radiotracer for detecting drug resistance in lymphoma cell lines.

To predict chemotherapy response using technetium-99m tetrofosmin and compare with p-glycoprotein and multidrug resistance related protein-1 expression in patients with untreated small cell lung cancer.

The aim of this study was to investigate the relationships among technetium-99m tetrofosmin (Tc-TF) accumulation in untreated small cell lung cancer (SCLC), the expression of P-glycoprotein (Pgp) and multidrug resistance related protein-1 (MRP1), and the response to chemotherapy in patients with untreated SCLC. Thirty patients with SCLC were studied with chest scintigraphy 15 to 30 min after intravenous injection of Tc-TF before chemotherapeutic induction. Tc-TF chest scans were interpreted both visually and quantitatively. The response to chemotherapy was evaluated upon completion of chemotherapy. Immunohistochemical analyses were performed on multiple non-consecutive sections of biopsy specimens to detect Pgp and MRP1 expression. Fifteen patients with good response to chemotherapy had a significantly higher incidence (100.0%) of positive Tc-TF chest single photon emission computed tomography (SPECT) findings and negative Pgp or MPR expression than 15 patients with poor response (20%) (P<0.05). The tumor/background (T/B) ratios were 1.8+/-0.3 and 1.2+/-0.3 for patients with good response and poor response, respectively (P<0.05). However, other prognostic factors (performance status, tumor size and stage) were not significantly related to Tc-TF chest scan findings and response to chemotherapy. Tc-TF chest scintigraphy correlated well with Pgp or MRP1 expression and accurately predicted the response to chemotherapy in patients with SCLC.

Predicting chemotherapy response and comparing with P-glycoprotein expression using technetium-99m tetrofosmin scan in untreated malignant lymphomas.

The purposes of this study were to predict the chemotherapy response of untreated malignant lymphomas (ML) using a technetium-99m tetrofosmin (Tc-TF) scan and to compare Tc-TF results with P-glycoprotein (Pgp) expression. Before undergoing chemotherapy, 25 patients with ML were enrolled in this study. Tc-TF scan was performed 10 min after intravenous injection of Tc-TF. Immunohistochemical analyses were performed on multiple sections of ML specimens to evaluate Pgp expression. The chemotherapy response was evaluated in the first 1-2 years after the completion of treatment. The mean tumor-to-background ratio of the 15 patients with good responses (3.23+/-0.56) was significantly higher than that of the ten patients with poor responses (1.18+/-0.11). All of the 15 patients with good responses had positive Tc-TF scan results, but negative Pgp expression. Among the ten patients with poor responses, all had negative Tc-TF scan results, but six had positive Pgp expression and four had negative Pgp expression. Significant differences in the incidences of good and poor responses were found between patients with positive Tc-TF scan results and patients with negative Tc-TF scan results and between patients with positive Pgp expression and patients with negative Pgp expression. No significant differences in the incidences of good and poor responses were found between Hodgkin's disease patients and non-Hodgkin's lymphoma patients, stage I-II patients and III-IV patients, patients aged >40 and patients aged < or =40 years, and patients with and without B symptoms. Compared with other prognostic factors, Tc-TF scan results and Pgp expression more accurately predict the chemotherapy response in patients with ML.

Detection of recurrent nasopharyngeal carcinomas with positron emission tomography using 18-fluoro-2-deoxyglucose in patients with indeterminate magnetic resonance imaging findings after radiotherapy.

PURPOSE: The aim of this study was to evaluate the effectiveness of positron emission tomography (PET) using 18-fluoro-2-deoxyglucose (FDG) to detect recurrent nasopharyngeal carcinomas (NPC) when magnetic resonance imaging (MRI) findings are indeterminate. PATIENTS AND METHODS: After radiotherapy, 28 NPC patients with indeterminate MRI findings were included. MRI, FDG-PET, and biopsy were performed at least 4 months after radiotherapy and within 1 week. The final results were based on histopathologic findings and a clinical follow-up of at least 6 months. RESULTS: For detecting recurrent NPC in indeterminate MRI findings, the sensitivity, specificity and accuracy of FDG-PET were 100.0%, 92.9% and 96.4%, respectively. CONCLUSIONS: Based on these results, we can recommend FDG-PET for detecting recurrent NPC when MRI findings are indeterminate.

Detecting parathyroid adenoma using technetium-99m tetrofosmin: comparison with P-glycoprotein and multidrug resistance related protein expression--a preliminary report.

The aim of this study was to investigate the relationships among technetium-99m tetrofosmin (Tc-TF) accumulation in parathyroid adenoma and the expression of P-glycoprotein (Pgp) or multidrug resistance related protein (MRP). Before operation, 33 patients with parathyroid adenomas (larger than 1.5 gm) were studied with parathyroid scintigraphy 10 minutes and 2 hours after intravenous injection of Tc-TF before operation. Immunohistochemical analyses (IHA) were performed on multiple nonconsecutive sections of operative parathyroid specimens to detect Pgp or MRP expression. According to the results of IHA, the 33 parathyroid adenomas were separated into four groups: (1) 2 adenomas with both positive Pgp and positive MRP expression, (2) 1 adenomas with positive Pgp but negative MRP expression, (3) 2 adenomas with negative Pgp but positive MRP expression, and (4) 28 adenomas with both negative Pgp and negative MRP expression. All of 28 adenomas in the group 4 could be detected by Tc-TF parathyroid imaging. All of 5 adenomas in the groups 1 to 3 could not be detected by TcTF parathyroid imaging (p < 0.05). Not only the size of parathyroid adenomas, but also significant Pgp or MRP expression limited the sensitivity of Tc-TF parathyroid imaging to localize parathyroid adenomas before operation.

Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings.

The major factor to influence localization of parathyroid adenomas is tumor size. P-glycoprotein (P-gp) expression in parathyroid adenomas has been considered to be an another possible factor to influence localization of parathyroid adenomas because false-negative studies have been reported with large tumors and true-positives reported with very small tumors in previous studies. The aim of this study was to characterize Tc-99m MIBI uptake and retention by parathyroid adenomas and to correlate this with cell surface expression of P-gp. Sixteen patients with parathyroid adenoma (larger than 1.5 gm) underwent dual-phase (10min and 2hr) Tc-99m MIBI parathyroid image immediately before parathyroid exploration. Tissues were obtained from normal and abnormal parathyroid glands and from the thyroid gland. Immunohistochemistry (IHC) was obtained with monoclonal antibodies to identify P-gp expression in all tissues. All of the 16 parathyroid adenomas and 32 normal control specimens (16 normal parathyroid and 16 normal thyroid specimens) were submitted for P-gp detection by IHC. The dual-phase Tc-99m MIBI parathyroid image accurately localized 14 parathyroid adenomas, but not the remaining 2 adenomas. The 14 parathyroid adenomas with significant Tc-99m MIBI uptake in delayed 2hr images revealed negative P-gp expression, but the 2 adenomas without significant Tc-99m MIBI uptake, as well as normal parathyroid and normal thyroid specimens, revealed positive P-gp expression when evaluated by IHC. Not only the size of parathyroid adenomas, but also significant P-gp expression limited the sensitivity of dual-phase Tc-99m MIBI parathyroid image to localize parathyroid adenomas before operation.

Comparison of technetium-99m methoxyisobutylisonitrile single photon emission computed tomography and computed tomography to detect recurrent or residual nasopharyngeal carcinomas after radiotherapy.

The diagnostic accuracy of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) single photon emission computed tomography (SPECT) of head and neck to differentiate between recurrent or residual nasopharyngeal carcinomas (NPC) and benign lesions after radiotherapy was evaluated, and compared with computed tomography (CT). Thirty-six NPC patients 4 months after radiotherapy underwent Tc-MIBI SPECT and CT of head and neck, as well as histopathological examination of nasopharyngeal biopsies. Based on the biopsy results, the sensitivity, specificity, and accuracy of CT were 73%, 88%, and 83%, respectively. The sensitivity, specificity, and accuracy of Tc-MIBI SPECT were 64%, 96%, and 86%, respectively. The sensitivity, specificity, and accuracy of combined Tc-MIBI SPECT and CT were 100%, 88%, and 92%, respectively. Tc-MIBI SPECT had a better specificity and a lower sensitivity to differentiate benign lesions from recurrent/residual NPC when compared with CT The combined use of CT and Tc-MIBI SPECT significantly increased accuracy compared with the single use of either Tc-MIBI SPECT or CT to differentiate benign lesions recurrent/residual NPC.

Technetium-99m methoxy-isobutyl-isonitrile chest single photon emission computed tomography to detect mediastinal lymph node metastasis in patients with non-small cell lung cancer: comparison with computed tomography.

This study evaluated the clinical role of Tc-99m-methoxyisobtylisonitrile (Tc-MIBI) single photon emission computed tomography (SPECT) of the chest in the detection of mediastinal lymph node (MLN) metastasis in patients with non-small cell lung cancer (NSCLC). Twenty-five patients with proven NSCLC were enrolled in this study. Each of the patients received computed tomography (CT) of the chest and Tc-MIBI SPECT of the chest for presurgical staging. A postsurgical pathologic diagnosis was made and these patients were evaluated for the study of mediastinal lymph nde (MLN) involvement. Meanwhile, 10 volunteers also accepted Tc-MIBI SPECT of the chest for comparison. The results showed that the diagnostic sensitivity, specificity and accuracy of Tc-MIBI chest SPECT were 81.8%, 85.7% and 84% and for chest CT they are 36.3%, 85.7% and 64%, respectively. Our results indicated that Tc-MIBI chest SPECT was more sensitive and accurate than chest CT in the evaluation and detection of MLN involvement in the NSCLC patients.

Value of 18F-fluoro-2-deoxyglucose positron emission tomography in the evaluation of recurrent colorectal cancer.

To evaluate the clinical value of positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG) in recurrent colorectal cancer, the records of 33 patients who underwent 34 FDG-PET scans were reviewed and compared with computed tomography (CT) and carcinoembryonic antigen (CEA). The final diagnosis was based on operative, histopathological findings or clinical follow-up > 1 year. FDG-PET detected all 15 patients with recurrent diseases (9 local recurrences, 4 lymphatic metastases, 2 hepatic metastases and 8 pulmonary metastases) and 1 primary lung cancer. However, there were 3 false positive cases. The overall sensitivity and specificity of FDG-PET were 100% and 83%, respectively. The sensitivity and specificity of CEA were 33% and 86%, respectively, for detecting recurrent colorectal cancer. Abdominal CT had a sensitivity and specificity of 78% and 61% for detecting local recurrence and detected one lymphatic and one hepatic metastasis. In conclusion, the FDG-PET was more accurate than CT and CEA for the detection of recurrent colorectal cancer. In addition, it accurately detected distant metastases or occult secondary malignancy and may affect clinical management.

Detection of cervical lymph node metastases of nasopharyngeal carcinomas with technetium-99m tetrofosmin single photon emission computed tomography and comparison with computed tomography.

The purpose of this study was to evaluate the usefulness of technetium-99m tetrofosmin (Tc-99m TF) single photon emission computed tomography (SPECT) in the detection of cervical lymph node (LN) metastasis in nasopharyngeal carcinomas (NPC), and to compare Tc-99m TF SPECT results with computed tomography (CT) findings. Fifty patients with biopsy-proven NPC and suspected cervical LN metastases underwent head and neck Tc-99m TF SPECT and CT to detect cervical LN metastases. Cervical LN metastases of 40 patients were confirmed by histopathological examination of biopsy samples. For 22 LN lesions with discordant results between Tc-99m TF SPECT and CT, Tc-99m TF SPECT could correctly detect 4 metastatic and 7 benign LN lesions while CT could correctly detect 5 metastatic and 6 benign LN lesions. Agreement positive results of Tc-99m TF SPECT and CT could correctly detect all of the 18 metastatic LN lesions. Tc-99m TF SPECT has a better specificity but a lower sensitivity for detecting cervical LN metastases in NPC when compared with CT. The combined use of Tc-99m TF SPECT and CT could significantly increase the accuracy of detect cervical LN metastases in NPC compared with the single use of either Tc-99m TF SPECT or CT.

Cerebral perfusion in patients with syndrome X: a single photon emission computed tomography study.

OBJECTIVE: To test the hypothesis that syndrome X is a systemic vascular disorder, the authors studied 40 patients with this diagnosis using technetium-99m hexamethylpropylene amine oxime and single photon emission computed tomography (SPECT) brain images. Twenty-three of 25 cases with definite myocardial perfusion defects diagnosed by thallium-201 myocardial perfusion SPECT also had multiple hypoperfusion areas in the brain versus 2 of 15 patients without thallium myocardial defects. The parietal lobes were the most common hypoperfusion areas, and cerebellum was the least common. Syndrome X is a systemic vascular disorder with a high incidence of hypoperfusion lesions of the brain and is usually coincident with myocardial defects.

Early predicting recurrent cervical cancer with combination of tissue polypeptide specific antigen (TPS) and squamous cell carcinoma antigen (SCC).

The establishment of new tumor marker combinations including strong lead-time effects in detecting recurrent cervical cancer appears to be warranted. This retrospective study includes 50 patients with recurrent squamous cell cervical cancer after operation or radiotherapy. The serial serum levels of the tumor markers tissue polypeptide specific antigen (TPS) and squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 78.5 U/L for TPS and 1.5 microg/L for SCC were selected according to the 95th percentile of serum concentrations measured in healthy control patients. Comparing with other monitoring modalities, SCC and TPS showed lead-time effective in 27 and 30 cases, respectively. This difference was not statistically significant. The combination of SCC and TPS provided lead-time effects in 42 cases. Our data indicate that combination of TPS and SCC is a valuable tool in the early predicting recurrent cervical cancer.

Detection of cervical lymph node metastases in nasopharyngeal carcinomas: comparison between technetium-99m methoxyisobutylisonitrile single photon emission computed tomography and magnetic resonance imaging.

We compared the effectiveness technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) of head and neck in evaluating cervical lymph node (LN) metastasis in nasopharyngeal carcinomas (NPC). Forty NPC patients with cervical LN metastases confirmed histopathologically underwent Te-99m MIBI SPECT and MRI of the head and neck to evaluate cervical LN metastases. For 16 LN lesions with discordant results between Tc-99m MIBI SPECT and MRI, Tc-99m MIBI SPECT could correctly detect 1 metastatic and 10 benign LN lesions as well as MRI could correctly detect 3 metastatic and 2 benign LN lesions. Agreement positive results of Tc-99m MIBI SPECT and MRI could correctly detect all of the remaining 24 metastatic LN lesions. Tc-99m MIBI SPECT has a better specificity but a lower sensitivity for detecting cervical LN metastases in NPC when compared with MRI. The combined use of Tc-99m MIBI SPECT and MRI could increase the accuracy compared with the single use of either Te-99m MIBI SPECT or MRI to detect cervical LN metastases in NPC.

The influences of blood glucose and duration of fasting on myocardial glucose uptake of [18F]fluoro-2-deoxy-D-glucose.

During the study of chest using positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG), a significant myocardial FDG uptake can prevent detection of the lesion that is located either behind or closely attached to the heart border. Two well-known and possible factors of myocardial FDG uptake are blood glucose level and fasting duration before FDG PET scanning. This study investigates whether the two factors are related to myocardial FDG uptake. Our study also explores the possibility of eliminating myocardial FDG uptake by controlling patients' blood glucose level and/or fasting duration. Whole-body FDG PET scans performed on 270 consecutive patients performed were reviewed. The study subjects were classified into four grades of myocardial FDG uptake according to the visual interpretation of the FDG PET image hard-copy films. For all study subjects, the blood sugar level and fasting duration before FDG injection were recorded. Then, the blood sugar levels and fasting duration were compared to the visual grade of myocardial FDG uptake for each study subject. About half of the study subjects showed graded 0 myocardial FDG uptake when the blood glucose levels were < or = 120 mg x dl(-1) or when the fasting duration was between 5 and 12 h. One hundred and thirty-one of the 142 (92%) patients with graded 0 uptake were asked to fast for > or = 4 h and had blood glucose levels < or = 120 mg x dl(-1). Based on our findings, we conclude that controlling the patients' blood glucose levels to < or = 120 mg x dl(-1) and at least 5 h fasting should be recommended to decrease myocardial FDG uptake.

Evaluating the changes in alveolar permeability and lung ventilation in patients with chronic renal failure after haemodialysis using 99mTc-DTPA radioaerosol inhalation lung scan.

Hypoxaemia occurring in patients with chronic renal failure (CRF) during haemodialysis (HD) has long been known. Several mechanisms of pathogenesis have been proposed. Before and after regular HD, lung ventilation (LV) and alveolar permeability (AP) were measured in 24 male patients with CRF (age, 61-75 years). LV and AP were determined by 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scan (99mTc-DTPA lung scan). The LV images were visually interpreted according to established criteria, including the presence or absence of an inhomogeneous distribution, inverted base to apex gradient and segmental hypoventilation. The degree of AP in the total right lung was presented as the clearance rate (K; %.min-1) of the time-activity curve from dynamic total right lung images. Ten male normal controls (age, 62-76 years) were enrolled in the study for comparison. Ten of 24 (42%) cases showed an inhomogeneous distribution and eight of 24 (33%) cases showed hypoventilation on equilibrium LV images. After regular HD for 5 h, no significant changes in the LV images were found. Before HD, the CRF patient group (K=1.14+/-0.36%.min-1) had a significantly faster clearance rate than that of normal controls (0.75+/-0.14%.min-1, P<0.05). Moreover, the clearance rate after HD was significantly slower (0.87+/-0.15%.min-1, P<0.05) than that before HD. CRF can predispose patients to LV change and AP damage. After HD, the damage to AP is significantly improved. However, after HD, the change in LV is not significant.

Comparison of quantitative 99mTc-HMPAO and 67Ga citrate lung scans in patients with active diffuse infiltrative lung disease.

Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders that predominantly affect the lung parenchyma and spare the airway. To objectively assess the degree of pulmonary vascular endothelium damage in active ILD, lung/liver uptake ratios (L/L ratios) on 99mTc hexamethylpropylene amine oxime (99mTc-HMPAO) lung scans were determined in 21 patients with active ILD. Meanwhile, the 67Ga citrate uptake index (GUI) on 67Ga lung scans was measured in order to evaluate the severity of lung inflammation in active ILD. The results show there were statistically significant differences between normal controls and patients with active ILD, as shown in the L/L ratio and GUI. However, when the patients were divided into two groups: (1) eight patients with normal chest X-ray findings, and (2) 13 patients with abnormal X-ray findings, there was no significant difference between groups 1 and 2 for the results of L/L ratio and GUI. In addition, no correlation between the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation was found. In conclusion, L/L ratios on 99mTc-HMPAO lung scans and GUI on 67Ga lung scans are different to the findings of chest X-rays and have the potential to objectively detect the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation in active IDL. However, the relationship between L/L ratio and GUI in active ILD is not significant.

Evidence of gallbladder function changes in hepatoma after transcatheter arterial embolization by quantitative Tc-99m DISIDA cholescintigraphy.

BACKGROUND/AIMS: Transcatheter arterial embolization is the treatment of choice for inoperable hepatocellular carcinoma. Gallbladder infarction following transcatheter arterial embolization has been reported, therefore, the gallbladder functions were studied using the quantitative Tc-99m DISIDA cholescintigraphy in the present study. METHODOLOGY: The gallbladder functions which were presented as the filling fraction and the ejection fraction in 24 patients with hepatoma before and after transcatheter arterial embolization. The patients were separated into two groups. Group 1: 12 patients received precystic artery transcatheter arterial embolization and group 2: 12 patients received postcystic artery transcatheter arterial embolization. RESULTS: After transcatheter arterial embolization, significantly decreased both gallbladder functions of filling fraction (61.2 +/- 7.4% and 48.3 +/- 6.5%) and ejection fraction (47.8 +/- 6.0% and 36.5 +/- 5.3%) were found in group 1 patients. However, no significant change of filling fraction (59.0 +/- 5.0% and 58.8 +/- 7.4%) and ejection fraction (49.9 +/- 2.4% and 49.3 +/- 5.7%) in group 2 patients. CONCLUSIONS: Impaired gallbladder functions were common in hepatoma patients who received precystic artery transcatheter arterial embolization, and Tc-99m DISIDA cholescintigraphy may be useful for evaluating the gallbladder functions in hepatoma patients who received transcatheter arterial embolization.

Using radionuclide esophageal emptying test to evaluate pneumatic dilatation effects for achalasia.

BACKGROUND/AIMS: Radionuclide esophageal emptying test using a solid meal is a simple, noninvasive, and physiologic test of esophageal function. METHODOLOGY: In this study, we evaluated esophageal emptying using an isotope-labeled solid meal (an egg salad sandwich labeled with 99mTc-MAA) in the assessment of pneumatic dilatation treatment in achalasia. Twenty achalasic patients (12 males, 8 females, age: 51.4 +/- 13.0 years) underwent esophageal emptying measurement before and after pneumatic dilatation. After treatment, the dysphagic symptoms of all patients improved. RESULTS: In comparison with the pretreatment test, the posttreatment retention fraction at 1, 5, 10, and 15 min were significantly lower (P < 0.001). CONCLUSIONS: The results suggest that radionuclide esophageal emptying test using a solid meal remains a useful objective study of esophageal function and may have an important future role in the follow-up evaluation of treatment for achalasia.

Diagnosis of coronary artery disease using dipyridamole thallium-201 imaging.

Dipyridamole thallium-201 imaging, using single-photon emission computed tomography, was evaluated for its safety and diagnostic efficacy in 109 patients with angiographically documented coronary artery disease and 35 normal subjects. The most common side effects after the intravenous administration of dipyridamole thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20 patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15 patients. Aminophylline was required to reverse the side-effects in 46 patients, and 45 of the 46 patients experienced complete relief of symptoms. Of the 109 patients with coronary artery disease, 104 had abnormal dipyridamole thallium images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had normal thallium images. The per patient specificity was 77%. The sensitivity and specificity for the individual vessels were 84% and 87% for the left anterior descending artery, 67% and 97% for the left circumflex artery, and 89% and 85% for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is a relatively safe noninvasive method and is an effective alternative to exercise thallium-201 scintigraphy for the diagnosis of coronary artery disease.