Hepatic clearance measured with (99m)Tc-GSA single-photon emission computed tomography to estimate liver fibrosis.

AIM: To evaluate the clinical utility of hepatic clearance (HC) measured with technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT) to estimate the degree of liver fibrosis. METHODS: Seventy-eight consecutive patients who underwent initial hepatectomy due to hepatocellular carcinoma were enrolled in this study. Indocyanine green clearance (ICG R15), quantitative indices estimated by (99m)Tc-GSA [the receptor index (LHL15 and HH15) and HC via SPECT analysis], and conventional liver function tests were performed before hepatectomy. Correlations among the quantitative indices for liver functional reserve, conventional liver function tests, and the degree of liver fibrosis were evaluated. RESULTS: The degree of liver fibrosis was correlated with ICG R15, HH15, LHL15, and HC. HC showed the best correlation with conventional liver function tests. According to multivariate analysis, HC and LHL15 were significant independent predictors of severe fibrosis. HC was the most valuable index for predicting severe fibrosis. CONCLUSION: HC measured with (99m)Tc-GSA SPECT is a reliable index for assessing liver fibrosis before hepatectomy.

(99m)Tc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors.

OBJECTIVES: Split renal function (SRF) estimated from the posterior view of (99m)Tc-diethylenetriaminepentaacetic acid planar scintigraphy (DTPA/P) is not sufficiently accurate even after correction for kidney depth by computed tomography (CT). To obtain more accurate SRF using (99m)Tc-DTPA, dynamic SPECT method was carried out for the initial 5 min after bolus injection of (99m)Tc-DTPA (DTPA/SPECT). Also SRF was evaluated from the renal volume measured by CT. We compared the results with (99m)Tc-dimercaptosuccinic acid SPECT (DMSA/SPECT). METHODS: In 60 consecutive live kidney donors, 30 DTPA/P, 30 DTPA/SPECT, 60 (99m)Tc-DMSA/SPECT, and 60 CT studies were performed. In the DTPA/P studies, SRF was calculated from the posterior image recorded during 2-3-min postinjection with attenuation correction for kidney depth measured by CT. In the DTPA/SPECT studies, SPECT images were acquired continuously for 5 min with a dual-headed gamma camera. In (99m)Tc-DMSA scintigraphy, DMSA/SPECT images were acquired 3-h postinjection. The SRF on both SPECT studies was calculated from the total counts of each kidney. In the DTPA/SPECT study, SRF was evaluated on the three images summed for 1 min: 1-2 min (DTPA/SPECT1-2), 2-3 min (DTPA/SPECT2-3), and 1-3 min (DTPA/SPECT1-3). In the CT examination, to assess the global renal volume, the axial images in the excretory phase were chosen. Renal contours were identified on each image, and the areas (cm(2)) of these regions were summed and multiplied by the slice thickness (10 mm) to yield global renal volume (ml). Right renal function from DTPA/P, DTPA/SPECT, and CT were compared with that from DMSA/SPECT as a reference. RESULTS: Correlation coefficients of the right renal function between DMSA/SPECT and DTPA/P, DTPA/SPECT2-3, and CT were 0.663, 0.849 and 0.907, respectively (P < 0.0001). The differences between DMSA/SPECT and DTPA/P, DTPA/SPECT2-3 and CT were 2.42 +/- 3.878, 0.867 +/- 1.672, and -0.421 +/- 1.077% (mean +/- SD), respectively. CONCLUSION: SRF derived from DTPA/SPECT showed a better correlation with DMSA/SPECT and significantly fewer errors (P < 0.05) than DTPA/P. A significant strong correlation was observed between SRF from DMSA/SPECT and CT, indicating the utility of CT renal volumetry for evaluating SRF.

Transient brain hyperperfusion detected with I-123 IMP SPECT in a patient with neuropsychiatric systemic lupus erythematosus.

We report the case of a 25-year-old woman with systemic lupus erythematosus. She complained of headache and left hemiparesis and was admitted to our hospital. She was in a coma after admission. Brain MRI showed no abnormalities, but brain single photon emission computed tomography showed diffuse hyperperfusion in the right frontal and temporal lobes. The calculated measured regional cerebral blood flow in the right hemisphere was increased to 40 to 55 mL/100 g/min, and that in the left was within the normal range of 25 to 35 mL/100 g/min. Two months later, the hyperperfusion was disappeared. The hyperperfusion could be explained by inflammatory changes.

Cerebral control of bladder storage in patients with detrusor overactivity.

OBJECTIVE: To identify the brain areas that control bladder storage by technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) with the Neurological Statistical Image Analysis software (NEUROSTAT) in patients with detrusor overactivity (DO). METHODS: SPECT scans were performed on 19 patients with DO. Eight patients with normal detrusor function, who had some storage symptoms of the lower urinary tract as the patients with DO, also had a SPECT scan, as controls. All the patients were male and right handed, and were scanned twice under two conditions: resting state and urine withholding state. NEUROSTAT was adopted to analyze the difference in brain--blood perfusion between groups and states. The results were displayed on Z score images at a significance threshold of P value of less than 0.05 with correction for multiple comparisons. RESULTS: No region reached the significant threshold in comparison with patients with DO and normal detrusor function in resting state. Significant increases in tracer activity in the right inferior frontal gyrus and the right middle temporal gyrus during urine withholding state as compared with resting state in patients with normal detrusor function were observed. Among the regions, the right inferior frontal gyrus was distinctly prominent at both Z score and the extent. The regions that were significantly activated in patients with normal detrusor function did not reach a significant threshold during urine withholding in patients with DO. CONCLUSION: The study indicated that the right inferior frontal gyrus and the right middle temporal gyrus, especially the right inferior frontal gyrus, played a role in the cerebral control of bladder storage, inhibiting the contraction of detrusor in urine storage.

Quantitative regional blood flow measurements in exercising leg skeletal muscle based on 99mTc-pertechnetate clearance.

BACKGROUND AND AIM: Skeletal muscle blood flow (SMBF) is a crucial indicator of impaired peripheral circulation. Although 133Xe has long been used for estimation of regional SMBF, its lipophilic and volatile nature hampers precise measurement. Therefore, we established an improved method based on 99mTc-pertechnetate ion (99mTcO-4) clearance. METHODS: Ten healthy male volunteers including five rugby players and five non-athletes (each group aged 25-35 years) received injection of 99mTcO-4 into the bilateral tibialis anterior muscles and gastrocnemius muscles (GCMs). The radioactivity of 99mTcO-4 before, during, and after toe-up or treadmill exercise was traced using a gamma-camera. Regional SMBF in absolute values (in ml/min/100 g muscle) was then calculated based on the half-time obtained from the time-activity curve. RESULTS: In both the groups, SMBF in tibialis anterior muscle changed similarly with values at the same levels. In contrast, SMBF in GCM showed marked difference between the two groups: in rugby players, SMBF in GCM returned to the baseline level (6.5+/-1.7, n=10) immediately after treadmill exercise, whereas that in non-athletes remained high (16.2+/-3.2, n=10). CONCLUSION: Regional SMBF measured by 99mTcO-4 clearance can indicate effectiveness of exercise training, and would be a diagnostic tool and prognostic indicator for use in patients with impaired peripheral circulation.

A compartment model analysis for investigation of myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy.

OBJECTIVE: The purpose of this study was to investigate the myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy (HCM) from dynamic SPECT through a compartment model analysis. METHODS: Twenty-four normal controls, seven patients with left ventricular hypertrophy (LVH) due to essential hypertension (eHT), and 30 patients with HCM were studied. 123I-BMIPP and 99mTc-tetrofosmin SPECT were performed. All the myocardium was divided into 13 segments, and a total of 390 segments of HCM were categorized into early, moderately and severely advanced HCM segments, based on these SPECT imaging. By using the myocardial and blood pool time-activity curves, BMIPP pharmacokinetics were analysed through a two-compartment model. We defined k1 and k2 as influx and outflux rate constants between blood and myocardial reversible component, and k3 as the specific uptake rate constant between myocardial reversible and irreversible compartments. RESULTS: The averages of k3 in HCM were higher than in normal. In contrast, the averages of k1/k2 in HCM were lower than in normal, and gradually decreased with progression of HCM. There are no significant differences in these indexes between normal controls and patients with LVH due to eHT. CONCLUSION: k3 might be a sensitive predictor for early detection of HCM, and k1/k2 could be a useful index to evaluate its progression. A mathematical compartment model analysis with a BMIPP SPECT study might be useful not only for identification of HCM in very early stage, but also for evaluation of the progression of HCM.

Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic resonance and scintigraphic findings.

Among natural disasters, a lightning strike is a rare but potentially life-threatening phenomenon. If victims survive a cardiac arrest due to instantaneous passage of an exceptionally high voltage electric charge through the whole body, they may be afflicted with various complications such as muscle necrosis resulting in acute renal failure. In this article, we report a case of a 54-year-old man with acute rhabdomyolysis of the left soleus muscle associated with a lightning strike. T2-weighted and short-tau inversion recovery MR images showed a high signal intensity in the left soleus muscle. A whole-body bone scintigram showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the left foot. MR and scintigraphic evaluations were very useful in depicting the site and extent of muscle damage. Since the patient showed a surprisingly high level of serum creatine kinase, the added information was very valuable for determining the patient's management.

Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging.

PURPOSE: To prospectively evaluate chemical shift magnetic resonance (MR) imaging for differentiating thymic hyperplasia from tumors of the thymus gland. MATERIALS AND METHODS: The institutional review board approved this study; informed consent was obtained and patient confidentiality was protected. The authors assessed 41 patients (17 male, 24 female; age range, 16-78 years) in whom thymic lesions were seen at chest computed tomography. Patients were assigned to a hyperplasia group (n=23) (18 patients with hyperplastic thymus associated with Graves disease and five with rebound thymic hyperplasia) and a tumor group (n=18) (seven patients with thymomas, four with invasive thymomas, five with thymic cancers, and two with malignant lymphomas). T2-weighted fast spin-echo and T1-weighted in-phase and opposed-phase MR images were obtained in all patients and visually assessed. A chemical shift ratio (CSR), determined by comparing the signal intensity of the thymus gland with that of the paraspinal muscle, was calculated for quantitative analysis. Mean CSRs for the patient groups and subgroups were analyzed by using Welch t and Newman-Keuls tests. P<.05 indicated a significant difference. RESULTS: The thymus gland had homogeneous signal intensity in all 23 patients in the hyperplasia group and in 12 of the 18 patients in the tumor group. The mean CSR (+/- standard deviation) was 0.614 +/- 0.130 in the hyperplasia group and 1.026 +/- 0.039 in the tumor group. Mean CSRs in the patients with a hyperplastic thymus and Graves disease, rebound thymic hyperplasia, thymoma, invasive thymoma, thymic cancer, and malignant lymphoma were 0.594 +/- 0.120, 0.688 +/- 0.154, 1.033 +/- 0.043, 1.036 +/- 0.040, 1.020 +/- 0.044, and 0.997 +/- 0.010, respectively. The difference in CSR between the hyperplasia and tumor groups was significant (P<.001). Mean CSRs in the hyperplasia subgroups were lower than those in the tumor subgroups (P<.001). All hyperplasia group patients had an apparent decrease in thymus gland signal intensity at chemical shift MR imaging; no tumor group patients had a decrease in thymus gland signal intensity. CONCLUSION: Chemical shift MR imaging can be used to differentiate thymic hyperplasia from thymic tumors.

Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model.

BACKGROUND AND AIM: In patients with a high risk of peritoneal dissemination of colon cancer, a treatment adjuvant to surgical resection would improve their prognosis. We aimed to determine whether radioimmunotherapy employing radiolabelled monoclonal antibody would work in this situation. METHODS: A murine model of peritoneal dissemination was established in female Balb/c nu/nu mice by intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody, radiolabelled with (131)I by the chloramine-T method was conducted intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively. RESULTS: Radioimmunotherapy at any timing improved survival of mice as compared with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(-1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained when radioimmunotherapy was conducted on day 0. CONCLUSION: These results indicate that intraperitoneal radioimmunotherapy may effectively kill colon cancer cells disseminated in the peritoneal cavity before formation of tumours and, therefore, may work as an adjuvant treatment to prevent peritoneal metastasis of colon cancer.

Cerebral activation during withholding urine with full bladder in healthy men using 99mTc-HMPAO SPECT.

UNLABELLED: The aim of this study was to identify the brain areas that control urinary continence in healthy men by 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT. METHODS: SPECT scans were performed on 15 right-handed healthy male volunteers, 24-45 y old. Each subject was scanned twice without movement in a supine position, and 444 and 555 MBq 99mTc-HMPAO were separately injected intravenously during the following 2 conditions: resting state with an empty bladder and urine-withholding state with a full bladder. The final image during urine withholding was obtained by subtracting the first scan data from the second scan data. The images were analyzed by statistical image analysis software and displayed on Z-score images at a significance threshold of P < 0.05 with correction for multiple comparisons. RESULTS: In the urine-withholding state, as compared with resting, there was a significant increase in tracer activity in the bilateral inferior frontal gyri and the right superior and the middle temporal gyri. Among the regions, the right inferior frontal gyrus was distinctly prominent. When the threshold value was decreased to P < 0.005 without correction, there was a vast network of cortical and subcortical regions involved during urine withholding. CONCLUSION: Our results suggest that the right inferior frontal gyrus plays an important role in brain control of urinary continence. This study also suggests that brain control of continence can be confirmed by statistical image analysis software using SPECT.

99mTc-sestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells.

OBJECTIVE: Technetium-99m sestamibi (MIBI) has been utilized to evaluate multi-drug resistance (MDR) phenomenon of malignant tumors and to predict chemotherapeutic effects on them. The current investigation examined the possibility of monitoring changes with respect to mRNA expression of multi-drug resistance associated protein (MRP) following antisense oligodeoxynucleotide (AS-ODN) treatment involving 99mTc-MIBI. METHODS: The human breast cancer MCF-7 cell line and its MDR-induced MCF-7/VP cell line were employed. Cell suspensions of the two cell lines at 1 x 10(4) cells/ml were inoculated in 24-well plates (0.2 ml/well) and incubated for one day. Antisense (AS) 20-mer phosphorothioate ODN complementary to the coding region of MRP mRNA and its sense (S) ODN were administered at final concentrations up to 25 microM, followed by a 5-day incubation. 99mTc-MIBI solution was added to each well and incubated for 30 min. Cellular 99mTc-MIBI uptake was corrected for protein concentration. MRP mRNA expression levels were analyzed via the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Cellular uptake of 99mTc-MIBI in MCF-7/VP cells was only 15% of that of MCF-7 cells. Following AS-ODN treatment at 25 microM for five days, 99mTc-MIBI uptake in MCF-7/VP cells increased 2.4-fold in comparison with non-treated control cells. 99mTc-MIBI uptake in MCF-7 cells was unaffected by AS-ODN administration. Sense ODN did not alter uptake in either cell line. RT-PCR confirmed reduction of MRP mRNA in MCF-7/VP cells following AS-ODN treatment. CONCLUSION: Effects of AS-ODN administration on MRP function can be monitored via assessment of cellular uptake of 99mTc-MIBI.

Anti-angiogenic therapy and chemotherapy affect 99mTc sestamibi and 99mTc-HL91 accumulation differently in tumour xenografts.

BACKGROUND: Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments. METHODS: Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions. RESULTS: 99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro. CONCLUSION: These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.

Evaluation of normal fatty replacement of the thymus with chemical-shift MR imaging for identification of the normal thymus.

PURPOSE: To clarify the influences of age and gender on normal fatty replacement of the thymus in childhood, adolescence, and early adulthood using chemical-shift MRI. MATERIALS AND METHODS: A total of 95 normal subjects (52 males and 43 females, mean age = 15.6 years, range = 7-25 years) who underwent chemical-shift MRI of the thymus were assessed prospectively. Signal intensity loss (SIL) of the thymus was determined by dividing the thymus/muscle ratio on the opposed-phase image by that on the in-phase image. We evaluated SIL for its correlation with age and gender, and assessed SIL of the thymus with uncommon morphological features. RESULTS: A significant correlation was found between SIL and age (r = 0.750, P < 0.001). There was no significant difference in SIL between the genders. No significant SIL was identified in any of the subjects aged 10 years or less. However, significant SIL was found in 70.8% of those aged 11-20 years, 100% of those aged 21 years or more, and 46.2% of subjects with uncommon morphological features of the thymus. CONCLUSION: Chemical-shift MRI can depict physiologic fatty infiltration within the normal thymus in subjects over 11 years of age. It is crucial to correlate these normal age-related findings with clinical cases in order to avoid misinterpretation.

Locoreginal radioimmunotherapy with 186Re-labeled monoclonal antibody in treating small peritoneal carcinomatosis of colon cancer in mice in comparison with 131I-counterpart.

The efficacy of locoregional radioimmunotherapy (RIT) in treating peritoneal tumors of colon cancer of <2 mm in diameter was examined at maximum tolerated doses, focusing the comparison between 186Re and 131I labeled to an anti-colorectal cancer IgG1. Estimated radiation doses to tumors were considerably higher with 186Re-RIT than with 131I-RIT. The advantage of 186Re-RIT decreased with decreasing tumor size, but 186Re-RIT delivered 1.6-times higher radiation to tumors of 1 mm. Consequently, 186Re-RIT attained better survival of mice than 131I-RIT or chemotherapy with 5-fluorouracil did. Therefore, locoregional 186Re-RIT may be an option in an adjuvant setting of colon cancer with high risk of peritoneal dissemination.

Impaired cardiac sympathetic nerve function in patients with Kawasaki disease: comparison with myocardial perfusion.

Kawasaki disease (KD) is a leading cause of CAD in children. The impairment of cardiac sympathetic nerve function (CSNF) in the adult patients with coronary artery disease (CAD) could often be seen. However, little is known concerning the impairment of CSNF in KD patients. We investigated CSNF and its relationship with myocardial perfusion in KD patients. Eleven children with KD and 4 controls were studied with 123I-metaiodobenzylguanidine (MIBG) and stressed 201Tl single photon emission computed tomography. By the findings on coronary artery angiography (CAG), the patients were divided into 2 groups: A, without stenosis; B, with significant stenosis and/or old myocardial infarction. CSNF was evaluated from the uptake of 123I-MIBG. While myocardial perfusion was evaluated from 201Tl uptake. The numbers of patients in the groups A and B were 7 and 4. Perfusion defect was found in 0, and 2 patients in group A (0%), and B (50%). 123I-MIBG defects were found in 1 and 4 patients in the group A (14%) and B (100%). There were excellent concordances between the finding of 201Tl and 123I-MIBG in group A. While in group B, the coronary territories with 123I-MIBG defects were significantly more than those with perfusion defects (p < 0.05). In KD patients, the impairment of CSNF might be subsequent to coronary artery stenosis and was more severe than the injury of myocardial perfusion.

Correct localization of epileptogenic focus with I-123 iomazenil cerebral benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with discordant ictal cerebral blood flow SPECT.

A 26-year-old female with intractable epileptic seizures was studied with I-123 iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated the location of the seizures to be in the left temporal lobe, where increased regional cerebral blood flow was noted in marked contrast to the inter-ictal SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal electrodes also suggested the left temporal lobe as the location of the seizures. On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal signal intensity in the right temporal lobe. Ictal EEGs recorded with intracranial electrodes revealed that abnormal electrical activity of the brain always emerged from the right temporal lobe and then propagated to the contralateral side. Based on the findings of intracranial EEGs, partial resection of the right anterior temporal lobe including hippocampus was performed. After the surgery, no seizure occurred. Pathological examination of the surgical specimens revealed hippocampal sclerosis. This case suggested that cerebral benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct localization of epileptogenic foci.

Limitations of (99m)Tc tetrofosmin in assessing reversal effects of verapamil on the function of multi-drug resistance associated protein 1.

BACKGROUND: Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours. METHODS: The uptake of Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells. CONCLUSION: These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.

Optimization of the uptake method for estimating renal clearance of 99mTc mercaptoacetyltriglycine.

OBJECTIVE: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts. METHODS: Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5 3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tønnesen's formula, and linear combination of scatter fraction and Tønnesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated. RESULTS: One-sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P<0.01) with one-sample clearance. The best correlation was observed in the model using renal depth determined by the combination of scatter fraction and Tønnesen's formulas, renal ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min (r=0.898, P<0.001). CONCLUSION: The renal uptake method for estimating the clearance of mercaptoacetyltriglycine can be improved by the processing conditions proposed here.

The radiotoxicity of 131I therapy of thyroid cancer: assessment by micronucleus assay of B lymphocytes.

UNLABELLED: We investigated cytologic radiation damage in thyroid cancer after (131)I therapy using micronucleus assay (MNA) of B lymphocytes exclusively, as opposed to our previous study in which MNA of all lymphocyte subsets was used. METHODS: We studied 22 thyroid cancer patients treated with 3.7 GBq of (131)I. Peripheral lymphocytes were harvested, and B lymphocytes were isolated by an immunomagnetic method and assayed for the frequency of micronuclei. RESULTS: The frequency of micronuclei among B cells after (131)I therapy was significantly increased relative to that in untreated control subjects, and the (131)I-induced increase in micronuclei frequency among B cells was significantly greater than that among all lymphocytes. CONCLUSION: Compared with the MNA of all lymphocytes, the MNA among specifically B cells may more sensitively detect cytologic radiation damage associated with (131)I therapy of thyroid cancer.