A randomized study of the effect of carbonated water prior to myocardial SPECT.

OBJECTIVE: In myocardial perfusion single-photon emission computed tomography (SPECT), abdominal activity often interferes with the evaluation of perfusion in the inferior wall, especially after pharmacological stress. In this randomized study, we examined the effect of carbonated water intake versus still water intake on the quality of images obtained during myocardial perfusion images (MPI) studies. METHODS: A total of 467 MIBI studies were randomized into a carbonated water group and a water group. The presence of intestinal activity adjacent to the inferior wall was evaluated by two observers. Furthermore, a semi-quantitative analysis was performed in the adenosine subgroup, using a count ratio of the inferior myocardial wall and adjacent abdominal activity. RESULTS: The need for repeated SPECT in the adenosine studies was 5.3% in the carbonated water group versus 19.4% in the still water group (p = 0.019). The inferior wall-to-abdomen count ratio was significantly higher in the carbonated water group compared to the still water group (2.11 ± 1.00 vs. 1.72 ± 0.73, p < 0.001). The effect of carbonated water during rest and after exercise was not significant. CONCLUSIONS: This randomized study showed that carbonated water significantly reduced the interference of extra-cardiac activity in adenosine SPECT MPI.

In vivo measurements of blood flow and bone metabolism in osteoarthritis.

With increasing age, there may be a decrease in femoral blood flow. In some patients, this may result in local ischaemia, which subsequently may lead to local degenerative changes. Consequently, bone blood flow may play an important role in the aetiology of osteoarthritis of the hip. Little is known about bone blood flow in the femoral head of patients with advanced hip osteoarthritis. The purpose of this study was to evaluate bone blood flow and metabolism in vivo in patients with osteoarthritis of the hip. Ten patients with symptomatic osteoarthritis of the hip were enrolled prospectively. Femoral bone blood flow and metabolism were measured using positron emission tomography together with H2(15)O and [(18)F]fluoride, respectively. Blood flow was 0.054 ± 0.032 mL cm(-3) min(-1) and 0.041 ± 0.012 mL cm(-3) min(-1) in symptomatic and contralateral femoral heads, respectively (p = 0.435). The net flux of fluoride from plasma to bone mineral (K i ) was significantly (p = 0.027) higher in the femoral head of the osteoarthritic hip (0.022 ± 0.012 mL cm(-3) min(-1)) than in that of the contralateral hip (0.007 ± 0.005 mL cm(-3) min(-1)). This study showed significant increase in bone metabolism in the proximal femur of patients with symptomatic osteoarthritis of the hip joint. There was no evidence of decreased blood flow.

Effect of the positron range of 18F, 68Ga and 124I on PET/CT in lung-equivalent materials.

PURPOSE: The aim of this study was to investigate the effect of positron range on visualization and quantification in (18)F, (68)Ga and (124)I positron emission tomography (PET)/CT of lung-like tissue. METHODS: Different sources were measured in air, in lung-equivalent foams and in water, using a clinical PET/CT and a microPET system. Intensity profiles and curves with the cumulative number of annihilations were derived and numerically characterized. RESULTS: (68)Ga and (124)I gave similar results. Their intensity profiles in lung-like foam had a peak similar to that for (18)F, and tails of very low intensity, but extending over distances of centimetres and containing a large fraction of all annihilations. For 90% recovery, volumes of interest with diameters up to 50 mm were required, and recovery within the 10% intensity isocontour was as low as 30%. In contrast, tailing was minor for (18)F. CONCLUSION: Lung lesions containing (18)F, (68)Ga or (124)I will be visualized similarly, and at least as sharp as in soft tissue. Nevertheless, for quantification of (68)Ga and (124)I large volumes of interest are needed for complete activity recovery. For clinical studies containing noise and background, new quantification approaches may have to be developed.

Multimodality imaging of carotid artery plaques: 18F-fluoro-2-deoxyglucose positron emission tomography, computed tomography, and magnetic resonance imaging.

BACKGROUND AND PURPOSE: This study's objective was to compare (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET), CT, and MRI of carotid plaque assessment. MATERIALS AND METHODS: Fifty patients with symptomatic carotid atherosclerosis underwent (18)F-FDG PET/CT and MRI. Correlations and agreement between imaging findings were assessed by Spearman and Pearson rank correlation tests, t tests, and Bland-Altman plots. RESULTS: Spearman rho between plaque (18)F-FDG standard uptake values and CT/MRI findings varied from -0.088 to 0.385. Maximum standard uptake value was significantly larger in plaques with intraplaque hemorrhage (1.56 vs 1.47; P=0.032). Standard uptake values did not significantly differ between plaques with an intact and thick fibrous cap and plaques with a thin or ruptured fibrous cap on MRI. (1.21 vs 1.23; P=0.323; and 1.45 vs 1.54; P=0.727). Pearson rho between CT and MRI measurements varied from 0.554 to 0.794 (P<0.001). For lipid-rich necrotic core volume, the CT-MRI correlation was stronger in mildly (10%) calcified plaques (Pearson rho 0.730 vs 0.475). Mean difference in measurement +/-95% limits of agreement between CT and MRI for minimum lumen area, volumes of vessel wall, lipid-rich necrotic core, calcifications, and fibrous tissue were 0.4+/-18.1 mm(2) (P=0.744), -41.9 +/-761.7 mm(3) (P=0.450), 78.4+/-305.0 mm(3) (P<0.001), 180.5+/-625.7 mm(3) (P=0.001), and -296.0+/-415.8 mm(3) (P<0.001), respectively. CONCLUSIONS: Overall, correlations between (18)F-FDG PET and CT/MRI findings are weak. Correlations between CT and MRI measurements are moderate to strong, but there is considerable variation in absolute differences.

Identification of a shine-through artifact in the trachea with (124)I PET/CT.

UNLABELLED: The presence of (124)I in tissue near the trachea can cause a phenomenon that might be called shine-through. The effect is due to high-energy positrons that cross the air-filled trachea and annihilate at the opposite tracheal wall, incorrectly suggesting uptake at that location. METHODS: We investigated shine-through using (124)I, (68)Ga, and (18)F PET/CT scans of a neck phantom. Additionally, we evaluated (124)I studies of 29 patients with differentiated thyroid cancer who underwent imaging for postsurgical staging. RESULTS: In the phantom studies with a 0.1-mL (124)I source, the relative intensity of shine-through decreased from 7% to nearly zero when the thickness of the positron-stopping layer was increased from 0.3 to 3.85 mm. In patients, shine-through was observed in 5 of the 29 studies, with intensities between 0.7% and 14%. CONCLUSION: Shine-through appears rather common in differentiated thyroid cancer. Recognition is important for identification of real lesions, calculation of uptake, and dosimetry.

Bone metabolism after total hip revision surgery with impacted grafting: evaluation using H2 15O and [18F]fluoride PET; a pilot study.

PURPOSE: To evaluate bone blood flow and bone formation in patients after total hip revision surgery with impacted bone grafting using H2 15O and [18F]fluoride positron emission tomography (PET). PROCEDURES: To asses bone blood flow and bone metabolism in bone allograft after impaction grafting, four patients treated with total hip revision surgery were enrolled prospectively in this study. Six patients scheduled for primary hip arthroplasties were included as a control group. The study protocol consisted of three H2 15O and [18F]fluoride PET scans in each patient. RESULTS: Bone blood flow increased significantly compared to the preoperative state in patients treated for primary hip arthroplasty. In patients undergoing revision surgery, bone blood flow was twofold to threefold higher compared to the preoperative state, but did not reach significance. Bone metabolism in patients undergoing revision was threefold higher 2 weeks postoperatively compared to the primary hip group. We found a significant correlation between Ki and bone blood flow. CONCLUSIONS: Allogeneic bone grafts induce a higher rate of local periprosthetic bone formation compared to periprosthetic bone formation after a primary total hip placement. In vivo coupling between bone blood flow and bone metabolism suggests that bone metabolism in allogeneic bone grafts may partly rely on bone blood flow adaptations.

Is subendocardial ischaemia present in patients with chest pain and normal coronary angiograms? A cardiovascular MR study.

AIMS: On the basis of an MRI study it has been suggested that subendocardial hypoperfusion is present in patients with cardiac syndrome X. However, further work is required to test whether these findings can be generalized. METHODS AND RESULTS: MRI was used to visually and semi-quantitatively assess subendocardial and subepicardial perfusion, at rest and during an infusion of adenosine, in 20 patients with angina pectoris and normal coronary angiograms. A myocardial perfusion index (MPI) was calculated using the normalized upslope of myocardial signal enhancement. An index for myocardial perfusion reserve (MPRI) was calculated by dividing the MPI values at maximal vasodilatation by the values at rest. The MPI in our study population increased significantly during adenosine infusion in both the subendocardium (from 0.091 +/- 0.020 to 0.143 +/- 0.030; P < 0.001) and the subepicardium (from 0.074 +/- 0.017 to 0.135 +/- 0.03; P < 0.001). The overall MPRI was 1.83 +/- 0.50. CONCLUSION: The results show that patients with chest pain and normal coronary angiograms had significant perfusion responses to adenosine in both the subendocardium and subepicardium. In the present study we found no evidence for subendocardial hypoperfusion in these patients.

Attenuation-corrected vs. nonattenuation-corrected 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography in oncology: a systematic review.

PURPOSE: To perform a systematic review and meta-analysis to determine the diagnostic accuracy of attenuation-corrected (AC) vs. nonattenuation-corrected (NAC) 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in oncological patients. PROCEDURES: Following a comprehensive search of the literature, two reviewers independently assessed the methodological quality of eligible studies. The diagnostic value of AC was studied through its sensitivity/specificity compared to histology, and by comparing the relative lesion detection rate reported with NAC-PET vs. AC, for full-ring and dual-head coincidence PET (FR- and DH-PET, respectively). RESULTS: Twelve studies were included. For FR-PET, the pooled sensitivity/specificity on a patient basis was 64/97% for AC and 62/99% for NAC, respectively. Pooled lesion detection with NAC vs. AC was 98% [95% confidence interval (95% CI): 96-99%, n = 1,012 lesions] for FR-PET, and 88% (95% CI:81-94%, n = 288 lesions) for DH-PET. CONCLUSIONS: Findings suggest similar sensitivity/specificity and lesion detection for NAC vs. AC FR-PET and significantly higher lesion detection for NAC vs. AC DH-PET.

Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I.

UNLABELLED: Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. METHODS: Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. RESULTS: The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. CONCLUSION: Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.

Diagnostic accuracy and interobserver variability of plain radiography, subtraction arthrography, nuclear arthrography, and bone scintigraphy in the assessment of aseptic femoral component loosening.

BACKGROUND: Plain radiography, subtraction arthrography, nuclear arthrography, and bone scintigraphy are imaging techniques commonly used to identify aseptic femoral component loosening. Controversy exists about the relative utility of these techniques. PATIENTS AND METHODS: We evaluated the diagnostic accuracy and interobserver reliability of the four techniques in 78 consecutive patients (mean age 70 years, range 29-88 years) referred for evaluation of their femoral hip prostheses. The standard evaluation protocol consisted of plain radiography followed by subtraction arthrography, nuclear arthrography, and bone scintigraphy. Surgery or the subsequent clinical course of the patient was used as gold standard. RESULTS: Overall, plain radiography had a sensitivity and specificity of 81 and 74%, respectively. Subtraction arthrography had a sensitivity of 47% and a specificity of 78%. Nuclear arthrography had a sensitivity of 69% and a specificity of 76%, and bone scintigraphy had a sensitivity of 88% with a specificity of 50%. CONCLUSION: We found considerable interobserver variability in all four techniques. Multivariate regression analysis revealed that bone scintigraphy and nuclear arthrography together made a significant contribution to the diagnosis when used in combination with plain radiography and are, when plain radiography is inconclusive, useful additional diagnostic techniques for the detection of femoral component loosening.

The value of contrast and subtraction arthrography in the assessment of aseptic loosening of total hip prostheses: a meta-analysis.

OBJECTIVE: To summarize and compare the diagnostic accuracy of contrast and subtraction arthrography in the assessment of aseptic loosening of total hip arthroplasties. DESIGN: This meta-analysis was performed using methods described by the Cochrane Methods Group on Systematic Reviews of Screening and Diagnostic Tests. We included original, English-language papers published between January 1975 to October 2004 that examined contrast-enhanced arthrography with or without subtraction for diagnosis of loosening of total hip prostheses. A qualitative and quantitative analysis was performed by two investigators. RESULTS: With regard to the acetabular component, pooled sensitivity and specificity for contrast arthrography was 70% (95% confidence interval, 52-84) and 74% (95% CI, 53-87), respectively. Subtraction arthrography had a significantly higher sensitivity of 89% (95% CI, 84-93) (p=0.01), with a similar specificity of 76% (95% CI, 68-82). For the femoral component, pooled sensitivity and specificity for contrast arthrography were 63% (95% CI, 53-72) and 78% (95% CI, 68-86). Pooled estimates for subtraction arthrography revealed a significantly higher sensitivity of 86% (95% CI, 74-93) (p=0.003). Specificity was 85% (95% CI, 77-91) and was similar to the data of contrast arthrography (p=0.23). CONCLUSION: Using the present data we found that the subtraction arthrography is a sensitive technique for detection of loosening of total hip prostheses, offering added value over contrast arthrography, especially for evaluation of the femoral component.

A comparison of radiographic and scintigraphic techniques to assess aseptic loosening of the acetabular component in a total hip replacement.

BACKGROUND: The diagnosis of a loose total hip prosthesis is often established with use of radiographic and nuclear medicine techniques, but there is controversy about the relative utility of plain radiography, subtraction arthrography, nuclear arthrography, and bone scintigraphy. In this retrospective study, we evaluated the sensitivity, specificity, and interobserver reliability of these imaging modalities in patients suspected of having aseptic loosening of the acetabular component. METHODS: From 1994 to 1999, eighty-six consecutive patients with pain after a total hip arthroplasty were evaluated for possible loosening of the components. The imaging evaluation included plain radiography followed by a one-day protocol that included bone scintigraphy, subtraction arthrography, and nuclear arthrography. For this study, two experienced nuclear medicine physicians and two experienced radiologists, all of whom were blinded with respect to the clinical pretest data and the clinical outcome, retrospectively interpreted the diagnostic images. The sensitivity and the specificity of each imaging modality were established by comparing the findings obtained with each technique with those found at surgery or during the subsequent clinical course of the patient. Interobserver variability was determined with the intraclass correlation coefficient. RESULTS: Plain radiography had a sensitivity of 85% (95% confidence interval, 71 to 94) and a specificity of 85% (95% confidence interval, 66 to 96) in detecting aseptic loosening of the acetabular component, but it had only fair interobserver variability (intraclass correlation coefficient, 0.37). For subtraction arthrography, the sensitivity was 72% (95% confidence interval, 57 to 84), the specificity was 70% (95% confidence interval, 50 to 86), and there was good interobserver variability (intraclass correlation coefficient, 0.71). For nuclear arthrography, the sensitivity was 57% (95% confidence interval, 41 to 71), the specificity was 67% (95% confidence interval, 46 to 84), and there was fair interobserver variability (intraclass correlation coefficient, 0.24). For bone scintigraphy, the sensitivity was 83% (95% confidence interval, 69 to 92), the specificity was 67% (95% confidence interval, 46 to 84), and there was moderate interobserver variability (intraclass correlation coefficient, 0.43). CONCLUSIONS: Plain radiography had the highest diagnostic accuracy in the evaluation of aseptic loosening of the acetabular component. The diagnostic accuracy was increased when plain radiography was combined with bone scintigraphy or subtraction arthrography. However, we found considerable interobserver variability in image interpretation, even with experienced radiologists and nuclear medicine physicians.

The sentinel node in cervical cancer: scintigraphy and laparoscopic gamma probe-guided biopsy.

The sentinel node (SN) procedure has been proven to be a valuable technique in the staging and treatment of a number of solid tumours. We evaluated the feasibility of SN biopsy with a laparoscopic gamma probe and dye guidance in 34 patients with clinically localised cervical cancer. After peritumoural injection of 140 MBq 99mTc colloidal albumin, dynamic and late static images were obtained. Just before the laparoscopic procedure, blue dye was injected. Blue and radioactive lymph nodes were excised followed by a regular lymphadenectomy. Lymphoscintigraphy revealed 70 SNs in 50 basins during dynamic imaging and 83 SNs in 63 basins at late imaging. SNs were visualised in 97% of the patients, bilaterally in 30 and unilaterally in three. Seventy-four of the 105 radioactive lymph nodes that were excised laparoscopically were considered to be SNs, 53 being blue as well, and were sent for frozen section. Nine foci that had been seen on scintigraphy could not be found either intraoperatively or in the remaining lymphadenectomy specimen. Four blue nodes were excised in three of five basins that had shown no foci during scintigraphy. In 17 basins of 12 patients, tumour-positive lymph nodes were found. In one of them a micrometastasis was found in the hysterectomy specimen while the lymphadenectomy did not contain any metastases (sensitivity 92%). Based on SN histology, the treatment was altered in nine patients (26%). We conclude that laparoscopic SN biopsy is feasible in cervical cancer and may result in custom-designed treatment strategies with a reduction in morbidity.

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.

PURPOSE: To prospectively evaluate the effect of adding whole-body (18)F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to conventional screening for distant metastases in patients with locally advanced breast cancer (LABC). PATIENTS AND METHODS: All women with LABC referred for participation in the LABC Spinoza trial were considered eligible for this study. Patients were included if chest x-ray, bone scan, liver ultrasound, or computed tomography scan performed by the referring physician failed to reveal distant metastases. They underwent whole-body FDG PET scanning before therapy. Patients with subsequently proven distant metastases were switched to alternative forms of chemotherapy, hormonal therapy, or both. RESULTS: Among the 48 patients evaluated with PET, 14 had abnormal FDG uptake, and metastases were suspected in 12. After simple clinical evaluation (plain x-ray, history), 10 sites that were suggestive of abnormality remained. Further work-up revealed that four sites were metastases. Proven false positivity occurred in one patient with sarcoidosis. In the other five patients, the reason for abnormal FDG uptake (liver, lung, bone) remained unclear, and patients were treated as planned. Eleven months later, distant metastases were found in one patient at sites unrelated to the previous FDG uptake. CONCLUSION: The addition of FDG PET to the standard work-up of patients with LABC may lead to the detection of unexpected distant metastases. This may contribute to a more realistic stratification between patients with true stage III breast cancer and those who are in fact suffering from stage IV disease. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment.

Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence camera in oncology.

The aim of this study was to evaluate the in vivo performance of a prototype dual-crystal [lutetium oxyorthosilicate (LSO)/sodium iodide (NaI)] dual-head coincidence camera (DHC) for PET and SPET (LSO-PS), in comparison to BGO-PET with fluorine-18 fluorodeoxyglucose (FDG) in oncology. This follows earlier reports that LSO-PS has noise-equivalent counting (NEC) rates comparable to partial ring BGO-PET, i.e. clearly higher than standard NaI DHCs. Twenty-four randomly selected oncological patients referred for whole-body FDG-PET underwent BGO-PET followed by LSO-PS. Four nuclear medicine physicians were randomised to read a single scan modality, in terms of lesion intensity, location and likelihood of malignancy. BGO-PET was considered the gold standard. Forty-eight lesions were classified as positive with BGO-PET, of which LSO-PS identified 73% (95% CI 60-86%). There was good observer agreement for both modalities in terms of intensity, location and interpretation. Lesions were missed by LSO-PS in 13 patients in the chest ( n=6), neck ( n=3) and abdomen ( n=4). The diameter of these lesions was estimated to be 0.5-1 cm. Initial results justify further evaluation of LSO-PS in specific clinical situations, especially if a role as an instrument of triage for PET is foreseen.

18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin's lymphoma.

A prospective study was performed, comparing gallium scintigraphy (67Ga) and positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (18FDG), to monitor the response of aggressive non-Hodgkin's lymphoma during treatment. 67Ga and 18FDG scans were performed in 26 patients after two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy. The scans were reviewed independently by four experienced nuclear physicians, who were blinded for the alternative scan technique and follow-up. Eleven out of 26 patients remained free from progression with a mean follow up of 25 +/- 5 months, whereas 14 patients relapsed, and one died of lung cancer. Interobserver variation was significantly greater for 67Ga than for 18FDG PET. Some 64% of patients who had a negative early restaging 18FDG PET remained free from progression versus 50% of patients with negative 67Ga scans. Only 25% of patients with a positive PET remained disease free versus 42% of 67Ga-positive patients. Time to progression was associated with 18FDG PET results, but not with those by 67Ga. 18FDG PET had better test characteristics than 67Ga for the evaluation of early response in aggressive non-Hodgkin's lymphoma patients.

Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study.

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between 736 and 1,588 depending on the (hospital) setting and the procurement of (18)FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile ( P=0.003). The average costs per patient in the CWU group were 9,573 and in the PET group, 8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective.

Cell cycle perturbations and radiosensitization effects in a human prostate cancer cell line.

PURPOSE: To test the hypothesis that radiation-induced, transient G2/M arrest could potentially sensitize tumor cells to a subsequent, well-timed radiation dose. METHODS: PC-3 human prostate cancer cells were treated using either radiotherapy or (186)Re-labeled hydroxyethylidene diphosphonate ((186)Re-HEDP) treatment in different combinations. The resulting cell cycle shift and clonogenic cell death were analyzed by DNA flow cytometry and colony forming cell assay, respectively. RESULTS: Radiation doses of 4 Gy and 8 Gy induced a transient G2/M arrest, with a maximum after approximately 16 h. The presence of 2 mM pentoxifylline effectively abrogated this radiation-induced G2 M arrest, confirming a cell-cycle checkpoint-mediated effect. A second dose of 4 Gy, timed at the height of the G2/M arrest, significantly increased clonogenic cell-kill compared to delivery after a suboptimal interval (10 h, 20 h or 25 h after the first radiation fraction). Moreover, timed second doses of 2 Gy, 3 Gy or 4 Gy yielded improved normalized treatment effects compared to non-pretreated control. Radionuclide treatment of PC-3 cells, using (186)Re-HEDP (0.74 MBq/ml and 1.48 MBq/ml; total dose: 4.1 and 8.2 Gy, respectively) also induced a dose-dependent G2/M accumulation, which sensitized the cells to a subsequent external radiation dose of 2 Gy or 4 Gy. The observed pattern of cell-cycle shift towards a predominance of the G2/M phase is in line with the lack of functional p53 in this cell line. CONCLUSIONS: Radiation-induced cell-cycle shift was shown to effectively confer increased radiosensitivity to prostate tumor cells. Optimally timed combination of radiotherapy and radionuclide therapy could thus significantly increase treatment efficacy.

Determinants of diagnostic performance of [F-18]fluorodeoxyglucose positron emission tomography for axillary staging in breast cancer.

OBJECTIVE: To prospectively investigate determinants of the accuracy of staging axillary lymph nodes in breast cancer using [F-18]fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: Patients with primary operable breast cancer underwent FDG PET of the chest followed by sentinel node biopsy (SNB, n = 47) and/or complete axillary lymph node dissection (ALND, n = 23). PET scans were independently interpreted by three observers in a blinded fashion with respect to the FDG avidity of the primary tumor and the axillary status. The results were compared to histopathological analyses of the axillary lymph nodes. Clinicians were blinded to the PET results. RESULTS: Axillary lymph node specimens and FDG PET scans were evaluated in 70 patients (59% cT1). Overall, 32 (46%) had lymph node metastases as established by SNB (18/47) or ALND (14/23), 20 of which were confined to a single node. The overall sensitivity of FDG PET was 25%, with a specificity of 97%. PET results were false-negative in all 18 positive SNBs and true-positive in 8/14 in the ALND group. The performance of FDG PET depended on the axillary tumor load and the FDG avidity of the primary tumor. Intense uptake in the primary tumor was found in only 57% of the patients, and this was independent of the size. There was excellent interobserver agreement of visual assessment of FDG uptake in primary tumor and axillary lymph nodes. CONCLUSIONS: The sensitivity of FDG PET to detect occult axillary metastases in operable breast cancer was low, and it was a function of axillary tumor load and FDG avidity of the primary tumor. Even though the clinical relevance of occult disease detected by SNB needs to be confirmed, it is suggested that FDG PET in these patients should be focused on exploiting its nearly perfect specificity and the potential prognostic relevance of variable FDG uptake.

How to use a gestalt interpretation for ventilation-perfusion lung scintigraphy.

UNLABELLED: The use of a so-called gestalt interpretation, an integration of different sets of criteria and the physician's own experience, has been advocated in the interpretation of lung scintigraphs of patients with clinically suspected pulmonary embolism. However, data on the reliability of this approach are limited. The aim of this study was to investigate the observer variability and accuracy of the gestalt interpretation of perfusion scintigraphy (combined with chest radiography) as well as the impact of adding ventilation scintigraphy and clinical pretest information. METHODS: Three experienced observers independently reviewed the chest radiograph and ventilation-perfusion scans of 101 consecutive patients with clinically suspected pulmonary embolism. All datasets were reviewed twice by each observer, using a visual analog scale to indicate the estimated probability of pulmonary embolism. The results of the gestalt interpretations were analyzed against the presence or absence of pulmonary embolism. RESULTS: All 3 gestalt interpretations had a good-to-excellent interobserver variability (intraclass correlation coefficient [ICC], 0.73-0.89), with similar intraobserver agreement (ICC, 0.76-0.95). The performance of all 3 readers was comparable. The areas under the curve (AUCs) of all 3 observers were high and similar (for observer 1, the AUCs were 0.96 [95% confidence interval (CI)], 0.93-1.00), 0.96 (95% CI, 0.93-1.00), and 0.95 (95% CI, 0.90-1.00), respectively, for the 3 gestalt interpretations). CONCLUSION: A gestalt interpretation is a useful classification scheme with good-to-excellent intra- and interobserver variability. However, the interpretation and the consequences of this result are dependent on the observer. Unexpectedly, the addition of information on ventilation scintigraphy and clinical information did not affect the overall assessment.