Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

Iodine-123-MIBG sympathetic imaging in Lewy-body diseases and related movement disorders.

Iodine-123-labeled metaiodobenzylguanidine (MIBG) has a history of over 20 years as a marker of myocardial sympathetic activity in Japan and has been used for various cardiac diseases. Aside from conventional utilities in patients with cardiac diseases, including ischemic heart diseases, cardiomyopathy, heart failure and diabetes, neurological disorders have recently been drawing special attention. The [(123)I]MIBG study showed markedly decreased myocardial uptake in Parkinson's disease, dementia with Lewy bodies and pure autonomic failure, which is a common feature of Lewy-body diseases. The MIBG study can be used for differentiating patients with extrapyramidal signs and dementia. The unique application of MIBG in movement disorders and related neurological diseases is one of its most common uses in Japan, and further studies are expected worldwide.

Optimization of radioimmunotherapy interactions with hyperthermia.

The efficacy of radioimmunotherapy (RIT) employing radiolabelled monoclonal antibodies (MAb) is currently limited in most solid tumours. The combination of local hyperthermia (HT) with RIT has the potential to enhance tumour targeting of MAb; moreover, this approach may add an antitumour effect to radioresistant hypoxic and S-phase cells and may inhibit the cells from repairing sublethal damage or potentially lethal damage caused by ionizing radiation. There are distinct types of protocols in this combination. Hyperthermic temperature and timing relative to RIT administration appear to affect the efficacy of the combination therapy. Responses to heating at any particular condition are not always the same among different tumour types. There are many papers describing influence of HT on the biodistribution of radiolabelled MAb, but only limited information is currently available on 'therapeutic' outcomes regarding the dependency of combination protocols. A previous study suggested that the best therapeutic improvement would be achieved when HT was combined immediately after the administration of MAb, which significantly increases the radiation absorbed dose to tumours and produces a uniform intratumoural dose distribution. Further therapeutic investigation should be required to reach the optimal protocol of combining these two modalities.

Hypoxia as a factor for 67Ga accumulation in tumour cells.

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 67Ga in the form of a 67Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 67Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N2/5% CO2 for 1 h at 37 degrees C. Cellular uptake of 67Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 67Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 67Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 67Ga citrate in N2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-transferrin relative to that of 67Ga citrate (P < 0.0001). Hypoxia did not affect the percentages of 67Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 67Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 67Ga in tumours, which is likely mediated by transferrin receptors.

Estimation of fractional liver uptake and blood retention of 99mTc-DTPA-galactosyl human serum albumin: an application of a simple graphical method to dynamic SPECT.

The objective of this study was to investigate clinical utility of a graphical method for estimating liver uptake and blood retention of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA; DTPA is diethylenetriaminepentaacetic acid) using dynamic single photon emission computed tomography (SPECT) data. When considering the kinetics of 99mTc-GSA, if it is assumed that (1) 99mTc-GSA distributes only between blood and liver, and (2) no metabolism of 99mTc-GSA occurs during the observation period, a plot of liver counts versus cardiac blood pool counts should, theoretically, be a straight line. From the slope and y intercept of a regression line, coefficients for converting count based liver and blood pool data to the per cent injected dose (%ID) can be calculated. The applicability of this method was tested on dynamic SPECT data from 30 patients with liver dysfunction. To validate this method, plasma concentrations (%ID/ml plasma) at 6, 15 and 30 min after the injection were estimated by this method and compared with the measured ones. To investigate the clinical significance of the per cent liver uptake, the value obtained by this method was compared with the results of conventional liver function tests, including serum albumin, the hepaplastin test, prothrombin time and indocyanine green clearance. In every data set, a plot of liver counts to cardiac blood pool counts was fitted well by a straight line (P<0.00001). Estimated plasma concentrations by this method showed good correlation with the measured ones at 6, 15 and 30 min after the injection (r=0.748, 0.838, 0.875, respectively; P<0.0001). The liver uptake determined by this method showed good correlation with the results of conventional hepatic function tests (P<0.002). The graphical method could provide an accurate estimate of %ID of 99mTc-GSA in blood without the need for blood sampling. The liver uptake determined by this method could be a simple but useful quantitative indicator of hepatic function.

Evaluation of left and right ventricular functional parameters with automatic edge detection program of ECG gated blood SPET.

An analysis program for ECG gated, blood pool, single photon emission tomography (SPET GBP) is available. This program permits the automatic evaluation of left and right ventricular function, but its reliability has not been thoroughly assessed. The objective of this investigation was to examine the reliability of the parameters derived from SPET GBP. Fifty-three patients who had undergone both SPET GBP and planar, ECG gated, blood pool scintigraphy (planar GBP) were enrolled in the study. Planar GBP was performed with a single-headed gamma camera. From a left anterior oblique projection, data were acquired at 24 frames/cardiac cycle with ECG gating during the equilibrium state. SPET GBP was carried out utilizing a triple-headed gamma camera, with 60 projection views over 360 degrees, with 60 s per view, in 16 frames/cardiac cycle. Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were calculated by using the analysis program. The reproducibility of these values and the correlation between SPET and planar GBP were assessed. To evaluate the effect of cut-off frequencies of a Butterworth filter, six different cut-off frequencies (order=8, 0.3-1.0 Nyquist) were tested with data obtained from 12 patients. The reproducibility of LVEF by SPET GBP was satisfactory (intra-observer, r=0.95; inter-observer, r=0.96), whereas reproducibility of RVEF by SPET GBP was fair (intra-observer, r=0.83; inter-observer, r=0.83). LVEF with SPET GBP was well correlated (y=1.1x+6.62, r=0.85, P<0.01) with LVEF readings of planar GBP. However, LVEF with SPET GBP was overestimated (mean difference of 12) in comparison with that of planar GBP. The RVEF derived from SPET GBP showed poor correlation (y=0.52x+33, r=0.53, P<0.01) with planar GBP. No significant effect of cut-off frequencies of Butterworth filters was evident in the calculation of LVEF and RVEF (P=0.48 and 0.67) with SPET GBP. It is concluded that SPET GBP with QBS is useful for the evaluation of LVEF. However, measurement of the RVEF showed lower reproducibility compared with measurement of the LVEF.

Differentiation of soft tissue haemangioma by 201Tl scintigraphy.

Radiological diagnosis of deep soft tissue is often difficult. In the present study, thallium-201 ( Tl) uptake into haemangiomas and deep malignant soft tissue tumours was investigated in order to assess its clinical utility. Tl scintigraphy was reviewed in four patients presenting with soft tissue haemangiomas. Early and delayed planar images, obtained at 15 min and 3 h following the intravenous injection of Tl (111 MBq), were examined. The Tl uptake ratio was calculated by dividing the count density of the tumour region of interest (ROI) by that of the background ROI. Results were compared with those of five cases of rhabdomyosarcoma and a single instance of angiosarcoma. All haemangioma lesions demonstrated increased Tl uptake in early images. However, Tl uptake in delayed images was markedly decreased. No significant differences were observed in the early uptake ratio between haemangiomas (1.60-2.72) and reference malignant tumours (1.48-2.45); however, the difference was significant in delayed images (range, 1.01-1.26 vs. 1.43-2.03, respectively) ( P<0.02). Deep soft tissue haemangiomas revealed Tl accumulation in early images; however, a rapid washout was observed in delayed images. This distinctive feature may facilitate the use of Tl scintigraphy in the diagnosis of haemangiomas.

A new method for measuring dynamic change of tracer distribution using dynamic single photon emission tomography with a slip-ring rotational gamma camera.

The clinical applicability of dynamic single photon emission tomograpy (SPET) using a dual-head gamma camera equipped with a slip-ring rotational mechanism, referred to as serial SPET, was examined in the present investigation. Serial SPET enables the production of tomographic images for any arbitrary time frame from an arbitrary range of data to 360 degrees. In a pre-clinical evaluation, a correlation between radioactivity concentration and serial SPET counts was evaluated in a phantom with continuous changes in 99mTc concentration. A differential value was obtained from each pair of SPET images; moreover, moving average approximation processing was investigated with respect to the elimination of noise in the data. In 11 and one patient presenting with cerebrovascular disease and meningioma, respectively, changes in SPET counts were evaluated when 99mTc ethyl cysteinate dimer (99mTc-ECD) was continuously administered at a constant rate in the resting state. Furthermore, in six of 11 subjects with cerebrovascular disease, changes occurring in SPET counts were examined by using acetazolamide loading while continuously administering 99mTc-ECD at a constant rate. Consequently, serial SPET enabled the evaluation of changes in radioactivity concentration over time in both the phantom and preliminary clinical studies. Data analysis by differential processing utilizing moving average approximation processing enabled the detection of minor changes in radioactivity concentration. An increase of 15.1+/-5.4% was observed in SPET counts of the unaffected cerebral hemisphere with acetazolamide loading. The response of the affected hemisphere was less prominent. These findings suggest that serial SPET would be an effective technique for the pharmacokinetic analysis of radiopharmaceuticals.

Intense 201 Tl uptake in giant-cell tumour of bone.

The aim of this study was to determine the characteristics and clinical usefulness of 201Tl scintigraphy in giant-cell tumour of bone (GCT). Twenty-one patients with histopathologically proven benign GCT (22 lesions; 18 primary and four recurrent) underwent 201Tl scintigraphy. We also studied conventional osteosarcoma (10 lesions), a very common primary malignant bone tumour; and chordoma in the sacrum (four lesions), an entity requiring differential diagnosis from GCT of the sacrum. Early and delayed planar imaging was performed at 15 min (early) and 3 h (delayed) after the intravenous injection of 201Tl chloride (111 MBq). The Tl uptake ratio was calculated by dividing the count density of the tumour region of interest (ROI) by that of the background ROI. All GCT lesions showed increased Tl uptake in both early and delayed images. The mean Tl uptake ratios of primary GCT were 4.7 (range, 2.0-11.1) in the early images and 2.2 (range, 1.4-3.6) in the delayed images, and those of recurrent lesions were 5.8 (range, 2.4-11.5) in the early images and 2.7 (range, 2.0-4.3) in the delayed images. There were no significant differences between the uptake ratios in GCT and osteosarcoma, but the values of GCT tended to be higher than those of osteosarcoma, 3.1 (range, 1.7-4.4) in the early images and 1.8 (range, 1.3-2.3) in the delayed images. Chordoma did not show appreciable Tl uptake: the uptake ratio was 1.19 (range, 0.98-1.5) in the early images and 1.1 (range, 1.0-1.3) in the delayed images. In GCT, a benign lesion, Tl scintigraphy demonstrated marked uptake in both primary and recurrent lesions with no exceptions, precluding the use of Tl scintigraphy for the differential diagnosis of GCT from malignant tumours. However, the Tl scintigraphy can be used for excluding GCT when no lesional Tl uptake is observed, and diagnosing recurrent lesions on post-operative follow-up.

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml x 100 g(-1) x min(-1) with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.

Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts.

Angiogenesis is critical to the growth and metastatic process of malignant tumors. An endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), displays anti-angiogenic and anti-tumorigenic effects. The purpose of this investigation was to determine whether exogenously administered 2-ME would enhance the efficacy of radioimmunotherapy (RIT). Experimental RIT with 4.63 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted in mice xenografted with LS 180 human colon cancer cells. 2-ME suspended in 0.5% carboxymethylcellulose was administered daily at a dose of 75 mg/kg per day. 2-ME administration suppressed tumor growth and improved the efficacy of RIT in comparison to RIT alone. Tumor volumes on day 13, expressed as a ratio relative to the initial volume, were 12.7 +/- 2.95 in the nontreated control, 4.73 +/- 0.89 with 2-ME, 3.05 +/- 0.37 with RIT and 0.97 +/- 0.20 with RIT+2-ME. Immunohistochemistry of tumor sections stained with an antibody against factor VIII demonstrated a decrease in microvessel number within tumors treated with 2-ME (7.9 +/- 0.8/200x field) as compared with that in control tumors (29.9 +/- 2.5). Cell proliferation assay at increasing concentrations of 2-ME showed direct cytotoxicity of 2-ME in vitro at 5 microM and greater. In conclusion, 2-ME enhanced the efficacy of RIT with 131I-A7 via inhibition of angiogenesis within the xenografts. The direct cytotoxicity of 2-ME appears to have contributed to this improvement. Anti-angiogenic therapy may prolong the dormancy of microscopic metastases while RIT may exterminate this population of cells. Therefore, the combined treatment may improve the therapeutic outcome of patients with disseminated cancer.

Assessment of left ventricular systolic and diastolic function based on the edge detection method with myocardial ECG-gated SPET.

The aim of this study was to determine the feasibility of assessing left ventricular systolic ejection and diastolic filling by the edge detection method with ECG-gated single-photon emission tomography (G-SPET) data. Fifty-two patients who had undergone both G-SPET and gated equilibrium blood pool scintigraphy (GBP) within an interval of 2 weeks were enrolled. For G-SPET, 740 MBq of technetium-99m methoxyisobutylisonitrile (MIBI) was injected at rest, and myocardial SPET was performed 60 min later using 360 degrees acquisition and 12 frames per cardiac cycle. In each frame, left ventricular volume was determined with automatic edge detection using a quantitative gated SPET program, and the time-volume curve was fitted by Fourier transform of the first to fourth harmonics. Ejection fraction (EF, %), peak ejection rate (PER, /s), peak filling rate (PFR, /s) and mean filling rate during the first third of diastolic time (1/3FRm, /s) were calculated from the fitted curve. These parameters were also calculated by means of GBP performed with 24 frames per cardiac cycle. Correlation coefficients in respect of EF, PER, PFR and 1/3FRm between G-SPET and GBP were 0.90 (P<0.001), 0.88 (P<0.001), 0.80 (P<0.001) and 0.82 (P<0.001), respectively. The correlations were good for EF, PER and 1/3FRm. Gated SPET dV/dt parameters were slightly lower compared with GBP values owing to the limited number of frames per cardiac cycle. It is concluded that left ventricular ejection and filling rates can be calculated using G-SPET with edge detection software, and in this study these parameters were significantly correlated with those derived using GBP. Diastolic abnormality on gated SPET study should be recognised as a positive finding, and appropriate gated SPET parameters should be further investigated.

Thymic lesions in patients with myasthenia gravis: characterization with thallium 201 scintigraphy.

PURPOSE: To assess thallium 201 ((201)Tl) single photon emission computed tomography (SPECT) for evaluation of thymic lesions associated with myasthenia gravis (MG), including lymphoid follicular hyperplasia (LFH) and thymoma. MATERIALS AND METHODS: (201)Tl SPECT and computed tomography (CT) were performed preoperatively in 46 patients with MG who had undergone thymectomy. SPECT was conducted 15 (early image) and 180 (delayed image) minutes after (201)Tl injection. Results were visually assessed, and (201)Tl uptake ratios (thymic lesion count density/lung count density) were measured for quantitative analysis. Uptake was analyzed among the normal thymus, LFH, and thymoma patient groups. RESULTS: Histopathologic results indicated a normal thymus, LFH, and thymoma in 19, 16, and 11 patients, respectively. Mean uptake ratios in the normal thymus, LFH, and thymoma were 0.96 (95% CI: 0.90, 1.03), 1.14 (95% CI: 1.04, 1.25), and 1.87 (95% CI: 1.56, 2.25), respectively, on early images and 1.09 (95% CI: 1.00, 1.18), 1.65 (95% CI: 1.48, 1.85), and 2.03 (95% CI: 1.65, 2.50), respectively, on delayed images. Thymoma showed more intense (201)Tl accumulation than did the normal thymus (P <.001) and LFH (P <.001) on early images. Both thymoma (P <.001) and LFH (P <.001) displayed more intense uptake than did the normal thymus on delayed images. CONCLUSION: (201)Tl SPECT can enable differentiation between normal thymus, LFH, and thymoma in patients with MG.

Experimental radioimmunotherapy with 186Re-MAG3-A7 anti-colorectal cancer monoclonal antibody: comparison with 131I-counterpart.

A murine IgG1 against a Mr 45 kD tumor-associated glycoprotein in human colorectal cancer, A7, was radiolabeled with 186Re by a chelating method with a mercaptoacetyltriglycine (MAG3). Its specific activity was 119 MBq/mg, which would be high enough for a therapeutic purpose, and its immunoreactivity was preserved well as was 131I-A7 labeled by the chloramine-T method. Growth of human colon cancer xenografts, 9.14 +/- 0.44 mm in diameter, in nude mice was significantly suppressed by an intravenous dose of 4.48 MBq of 186Re-A7. The therapeutic outcome with 186Re-A7 was better than that with 4.63 MBq of 131I-A7. Toxicity of treatments assessed by body weight change was similar with both conjugates. These results are likely caused by the tumor size and more favorable physical properties of 186Re than those of 131I.

Clinical approach to renal study incidental to 99mTc-MDP bone scintigraphy.

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment.

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.

Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary involvement.

PURPOSE: Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with (i) extent of scleroderma, (ii) duration of disease, (iii) index of anti-topoisomerase I antibody (topo I), and (iv) pulmonary involvement. METHODS: A multiple-swallow test was performed in 47 patients with SSc in the supine position with 99mTc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. RESULTS: Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p < 0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p < 0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DLCO) had higher RRs than those with normal %DLCO (40.5% vs. 19.6%; p = 0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p < 0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p < 0.00005). CONCLUSION: Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis.

Methylxanthine sensitization of human colon cancer cells to 186Re-labeled monoclonal antibody.

UNLABELLED: Tumor cells lacking the functional p53 suppressor gene may arrest at the G2 phase of the cell cycle after exposure to ionizing radiation, resulting in increased radioresistance. Methylxanthines (MTXs), such as pentoxifylline (PTX) or caffeine (CAF), can inhibit the G2-phase checkpoint arrest of damaged cells and thus radiosensitize them. However, the effect of MTX in cells irradiated with low-dose-rate beta-emission is not well understood. METHODS: A clonogenic assay was performed with LS180 human colon cancer cells lacking the functional p53 suppressor gene. Cells were irradiated with increasing concentrations of 186Re-mercaptoacetyltriglycine (186Re-MAG3)-labeled A7 monoclonal antibody against colorectal cancer (0-925 kBq/mL) at 37 degrees C in 5% CO2 for 24 h in the presence or absence of PTX (0-2 mmol/L) or CAF (0-5 mmol/L). The enhancement ratio (ER) with MTX was calculated as a ratio of 50% cell-killing concentration of 186Re-MAG3-A7 in control cells to that in cells treated with PTX or CAF. The cell cycle distribution was analyzed with a flow cytometer. RESULTS: The concentration of 50% cell kill was 474 kBq/mL 186Re-MAG3-A7. Both PTX and CAF dose dependently enhanced the cytotoxicity of 186Re-MAG3-A7: ERs of 0.5 mmol/L PTX, 2 mmol/L PTX, 1 mmol/L CAF, and 5 mmol/L CAF were 1.50, 2.18, 1.54, and 2.63, respectively. Flow cytometry showed that the percentage nonirradiated cells in the G2/M phase of the cell cycle was 11.3% +/- 1.66%. On the other hand, cells exposed to 186Re-MAG3-A7 accumulated in the G2/M phase of the cell cycle (40.2% +/- 1.46%), which was inhibited by the presence of 1 mmol/L PTX (19.8% +/- 8.12%) or 2 mmol/L CAF (26.9% +/- 6.21%). CONCLUSION: Cellular modulation of the cell cycle with PTX and CAF radiosensitized LS180 colon cancer cells exposed to 186Re radiation.

Technetium-99m-tetrofosmin would be a substrate for multidrug resistance-associated protein (MRP): comparison between a leukemia cell line with high MRP gene expression and its parental cell line.

UNLABELLED: The kinetics of cellular accumulation and retention of technetium-99m-tetrofosmin (99mTc-TF) were investigated in wild type HL60/WT cell line and in its doxorubicin-resistant HL60/DOX cell line with multidrug resistance-associated protein (MRP), but without P-gp overexpression, to determine whether 99mTc-TF is a substrate for MRP. METHODS: The accumulation and washout of 99mTc-TF were observed in both cell lines at 37 degrees C. The effect of verapamil on the kinetics was also assessed. RESULTS: 99mTc-TF net accumulation was significantly lower in HL60/DOX (1.35 +/- 0.23%) than in HL60/WT (12.79 +/- 0.47%) at 60 min (P < 0.001). Three minutes after exchanging the incubation solution to the tracer-free medium, only 18.20 +/- 0.34% of 99mTc-TF remained in HL60/DOX, whereas 84.74 +/- 0.65% did in HL60/WT (P < 0.001). In the presence of 10 microM verapamil, 99mTc-TF net accumulation in HL60/DOX was 302% of the control and the washout was significantly delayed. CONCLUSION: 99mTc-TF would be a substrate for MRP and 99mTc-TF may be used as a functional imaging agent of MRP in vivo.

[Improvement of 99mTc-pyrophosphate scintigraphy in detection of acute myocardial infarction: combined with 99mTc-tetrofosmin].

BACKGROUND: 201Tl and 99mTc-pyrophosphate (PYP) dual scintigraphy is daily used in the detection of acute myocardial infarction (AMI). However, 201Tl is not available on emergent situation. We proposed a new method for detection of AMI combined 99mTc-PYP with 99mTc-tetrofosmin (TF). METHODS: 99mTc-PYP (740 MBq) was administered to 25 patients with AMI, and 3.5 hours later, planar imaging (PYP planar) and SPECT were performed (PYP-SPECT). Immediately after cessation of PYP-SPECT, 99mTc-TF (370-740 MBq) was injected and 5 minutes later SPECT was performed in the same position (TF-SPECT). PYP-SPECT and TF-SPECT were reconstructed in the same geometric status to permit superimpose of PYP-SPECT and TF-SPECT images. Two experts and 2 beginners of nuclear medicine physician interpreted the images in three ways; PYP planar image only, PYP-SPECT, and PYP-SPECT with TF-SPECT. RESULTS: PYP-SPECT combined with TF-SPECT shows 100% detectability of the AMI lesions, which is significantly higher than other two methods in both experts and beginners. CONCLUSION: PYP-SPECT combined with TF-SPECT is a powerful method for detection of AMI.