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.

Comparison of 99mTc-MIBI uptakes on planar images with those in excised rats organs.

The precision with which images reflect tracer uptake in the myocardium has been studied. Additionally, the degree to which Tc methoxyisobutylisonitrile (99mTc-MIBI) in the liver gave the effect to a myocardial image has been examined. After administering Tc-MIBI to normal male rats, we compared the myocardial uptakes obtained using a gamma camera with the actual uptakes in the excised organs. Twenty-nine rats were used. Following imaging, the anterior view at 5, 10, 15, 30, 45, 60, 90 and 120 min after administration of the tracer, uptakes in the heart, lung, liver and blood were estimated with a well-type scintillation counter (WC) and represented as the percentage of the injected dose per gram of tissue (%ID/g). The regions of interest (ROIs) were placed on planar images (PI) and the uptake in each organ was estimated as the percentage of the injected dose per pixel (%ID/pixel). The ratios of PI-to-WC and heart-to-organ were also evaluated. Cardiac uptake with WC was maximum (1.581%+/-1.893%) at 10 min post-injection. On the other hand, that with PI was maximum (1.493%+/-0.598%) at 45 min post-injection, but there were significant differences between both measurements (PI/WC ratio: about 1.0 time). Pulmonary uptake with WC was the maximum at 5 min (0.808%+/-0.015%) post-injection, and decreased gradually. PI measurement showed the maximum value at 45 min (0.760%+/-0.012%). Hepatic uptake with WC was the maximum at 30 min (0.594%+/-0.254%). On the other hand, PI measurement showed the same pattern with WC, but these values were higher value than WC as the whole. PI measurement showed higher uptakes in each organ than WC measurement. It was concluded that uptakes or the heart-to-organ ratio obtained clinically with PI might not represent a value that is always accurate.

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.

A case of double cancers with myocardial metastasis mimicking acute myocardial infarction both on an electrocardiogram and on Tc-99m-MIBI myocardial SPECT.

We report a rare case of double cancers with myocardial metastasis presenting acute myocardial infarction (AMI)-like findings both on an electrocardiogram (ECG) and on Tc-99m-MIBI myocardial SPECT. The ECG showed abnormal Q-waves and ST-segment elevation in leads V1-V4, and Tc-99m-MIBI SPECT showed a photon deficient area in the anteroseptum. These findings were suggestive of AMI, but the patient had been simultaneously suffering from two adenocarcinomas, which were lung cancer and gastric cancer, and consecutive ultrasonic cardiography (UCG) demonstrated a growing mass lesion in the septal aspect of the left ventricle. After a month he died of severe heart failure. The histological diagnosis of a specimen of the cardiac mass lesion was invasive adenocarcinoma infiltrating to the heart, which revealed that the myocardial metastasis had mimicked AMI. This case shows that it is difficult to distinguish between myocardial infarction and myocardial metastasis with myocardial perfusion SPECT. It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents AMI-like findings.

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.

(99m)Tc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: comparison with coronary flow reserve measured by Doppler flowire.

UNLABELLED: The aim of the study was to investigate the increase in myocardial (99m)Tc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation. METHODS: For calculation of the increase in (99m)Tc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula [abstract: see text] where Cm(h)(t) and Cm(b)(t) are myocardial counts on the tomographic image, and Cb(b)(tau) and Cb(h)(tau) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients. RESULTS: Sestamibi retention increased as coronary flow velocity increased but plateaued at >2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X(2) (r = 0.82). CONCLUSION: In humans, the increase in (99m)Tc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging.

Accuracy of ventricular volume and ejection fraction measured by gated myocardial SPECT: comparison of 4 software programs.

UNLABELLED: Gated myocardial perfusion SPECT has been used to calculate ejection fraction (EF) and end-diastolic volume (EDV) and has correlated well with conventional methods. However, the comparative accuracy of and correlations across various types of gated SPECT software are not well understood. METHODS: Mathematic phantoms of cylindric-hemispheric hybrid models, ranging in volume from 34 to 266 mL, were generated. The clinical cases consisted of 30 patients who participated in a radionuclide angiography and gated blood-pool (GBP) study in addition to undergoing (99m)Tc-sestamibi gated SPECT. Four kinds of software, Quantitative Gated SPECT (QGS), the Emory Cardiac Toolbox (ECT), 4D-MSPECT, and Perfusion and Functional Analysis for Gated SPECT (pFAST) were used to compute EF and EDV, and the results were analyzed by multiple comparisons tests. Patients were classified into 4 groups (i.e., no defect, small defect, large defect, and small heart) so that factors affecting variation could be analyzed. RESULTS: In mathematic models > or = 74 mL, volume error was within +/-15%, whereas for a small volume (34 mL), QGS and 4D-MSPECT underestimated the volume and pFAST overestimated it. The respective intra- and interobserver reproducibility of the results was good for QGS (r = 0.99 and 1.00), ECT (r = 0.98 and 0.98), and 4D-MSPECT (r = 0.98 and 0.98) and fair for pFAST (r = 0.88 and 0.85). The correlation coefficient for EF between gated SPECT and the GBP study was 0.82, 0.78, 0.69, and 0.84 for QGS, ECT, 4D-MSPECT, and pFAST, respectively. The correlation coefficient for EDV between gated SPECT and the GBP study was 0.88, 0.89, 0.85, and 0.90, respectively. Although good correlation was observed among the 4 software packages, QGS, ECT, and 4D-MSPECT overestimated EF in patients with small hearts, and pFAST overestimated the true volume in patients with large perfusion defects. Correlation coefficients among the 4 kinds of software were 0.80-0.95 for EF and 0.89-0.98 for EDV. CONCLUSION: All 4 software programs showed good correlation between EF or EDV and the GBP study. Good correlation was observed also between each pair of quantification methods. However, because each method has unique characteristics that depend on its specific algorithm and thus behaves differently in the various patient subgroups, the methods should not be used interchangeably.

Phantom studies for estimation of defect size on cardiac (18)F SPECT and PET: implications for myocardial viability assessment.

UNLABELLED: SPECT with (18)F-FDG has emerged as an alternative to dedicated PET for the assessment of myocardial viability. However, whether FDG SPECT can reliably quantify the extent of viable and scarred myocardium is uncertain. The aim of this study was to investigate whether SPECT with an (18)F-labeled agent would provide information on defect size similar to that provided by dedicated PET. METHODS: Imaging was performed using an elliptic cylinder chest phantom with simulated bone, lung, mediastinum, liver, and heart. (18)F was administered into the myocardium, mediastinum, right and left ventricular cavities, and liver. Plastic inserts (n = 11) ranging in size from 2% to 60% of the myocardium were used to simulate transmural myocardial infarctions. The chest phantom was imaged with a dedicated PET camera and with a double-head SPECT camera equipped with ultra-high-energy collimators. Both SPECT and PET data were analyzed using a semiquantitative polar map approach. Defects were quantified using various cutoff thresholds ranging from 30% to 80% of peak activity and were expressed as a percentage of the left ventricular myocardium. Defect size as measured by SPECT or PET was compared with true defect size. RESULTS: The measured SPECT defect size was highly variable depending on the cutoff used, whereas PET defect size was relatively constant over the range of cutoffs tested. The mean absolute difference between measured and true defect sizes was minimal at a cutoff of 50% of peak activity for both SPECT (3.3% +/- 3.3%) and PET (2.7% +/- 2.5%). For this threshold, both SPECT and PET measurements showed an excellent correlation with true defect size (r = 0.98 for SPECT and 0.99 for PET). The correlation between SPECT and PET measurements was also excellent (r = 0.99; P < 0.01). CONCLUSION: If an appropriate threshold is used to define a defect, SPECT with an (18)F-labeled agent can accurately measure defect size similarly to the manner of PET.

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.

Nuclear imaging of bone tumors: thallium-201 scintigraphy.

(201)Tl scintigraphy provides important information for the management of patients with bone tumors. Although the role for staging the disease of bone tumors and for differentiation of benign from malignant lesions is limited, (201)Tl scintigraphy reflects the disease activity after treatment and it should be used to determine the treatment response and for early diagnosis of recurrence. Baseline study is essential for future reference to evaluate the response to preoperative chemotherapy and to detect recurrence after surgery. Sequential (201)Tl scintigraphy before and after treatment is useful in assessing the grade of response of the tumor to chemotherapy. The early prediction of chemotherapeutic effect by (201)Tl scintigraphy during treatment will affect the management of patients who do not respond to the therapy. This is of special importance to determine whether the patient needs an amputation or a limb-salvage surgery.

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.