18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study.

PURPOSE: F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and MRI are used for detecting liver metastases from uveal melanoma. The introduction of new treatment options in clinical trials might benefit from early response assessment. Here, we determine the value of FDG-PET/CT with respect to MRI at diagnosis and its potential for monitoring therapy. MATERIAL AND METHODS: Ten patients with biopsy-proven liver metastases of uveal melanoma enrolled in a randomized phase III trial (NCT00110123) underwent both FDG-PET coupled with unenhanced CT and gadolinium-diethylene triamine pentaacetic acid-enhanced liver MRI within 4 weeks. FDG-PET and MRI were evaluated blindly and then compared using the ratio of lesion to normal liver parenchyma PET-derived standardized uptake value (SUV). The influence of lesion size and response to chemotherapy were studied. RESULTS: Overall, 108 liver lesions were seen: 34 (31%) on both modalities (1-18 lesions/patient), four (4%) by PET/CT only, and 70 (65%) by MRI only. SUV correlated with MRI lesion size (r=0.81, P<0.0001). PET/CT detected 26 of 33 (79%) MRI lesions of more than or equal to 1.2 cm, whereas it detected only eight of 71 (11%) lesions of less than 1.2 cm (P<0.0001). MRI lesions without PET correspondence were small (0.6±0.2 vs. 2.1±1.1 cm, P<0.0001). During follow-up (six patients, 30 lesions), the ratio lesion-to-normal-liver SUV diminished in size-stable lesions (1.90±0.64-1.46±0.50, P<0.0001), whereas it increased in enlarging lesions (1.56±0.40-1.99±0.56, P=0.032). CONCLUSION: MRI outweighs PET/CT for detecting small liver metastases. However, PET/CT detected at least one liver metastasis per patient and changes in FDG uptake not related to size change, suggesting a role in assessing early therapy response

Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine.

PURPOSE: Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations. METHODS: Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment. RESULTS: The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline. CONCLUSION: FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles

Implementation of Quality Systems in Nuclear Medicine: Why It Matters. An Outcome Analysis (Quality Management Audits in Nuclear Medicine Part III).

The International Atomic Energy Agency (IAEA) developed a comprehensive program-Quality Management Audits in Nuclear Medicine (QUANUM). This program covers all aspects of nuclear medicine practices including, but not limited to, clinical practice, management, operations, and services. The QUANUM program, which includes quality standards detailed in relevant checklists, aims at introducing a culture of comprehensive quality audit processes that are patient oriented, systematic, and outcome based. This paper will focus on the impact of the implementation of QUANUM on daily routine practices in audited centers. Thirty-seven centers, which had been externally audited by experts under IAEA auspices at least 1 year earlier, were invited to run an internal audit using the QUANUM checklists. The external audits also served as training in quality management and the use of QUANUM for the local teams, which were responsible of conducting the internal audits. Twenty-five out of the 37 centers provided their internal audit report, which was compared with the previous external audit. The program requires that auditors score each requirement within the QUANUM checklists on a scale of 0-4, where 0-2 means nonconformance and 3-4 means conformance to international regulations and standards on which QUANUM is based. Our analysis covering both general and clinical areas assessed changes on the conformance status on a binary manner and the level of conformance scores. Statistical analysis was performed using nonparametric statistical tests. The evaluation of the general checklists showed a global improvement on both the status and the levels of conformances (P < 0.01). The evaluation of the requirements by checklist also showed a significant improvement in all, with the exception of Hormones and Tumor marker determinations, where changes were not significant. Of the 25 evaluated institutions, 88% (22 of 25) and 92% (23 of 25) improved their status and levels of conformance, respectively. Fifty-five requirements, on average, increased from nonconformance to conformance status. In 8 key areas, the number of improved requirements was well above the average: Administration & Management (checklist 2); Radiation Protection & Safety (checklist 4); General Quality Assurance system (checklist 6); Imaging Equipment Quality Assurance or Quality Control (checklist 7); General Diagnostic (checklist 9); General Therapeutic (checklist 12); Radiopharmacy Level 1 (checklist 14); and Radiopharmacy Level 2 (checklist 15). Analysis of results related to clinical activities showed an overall positive impact on both the status and the level of conformance to international standards. Similar results were obtained for the most frequently performed clinical imaging and therapeutic procedures. Our study shows that the implementation of a comprehensive quality management system through the IAEA QUANUM program has a positive impact on nuclear medicine practices

Suppressing bladder artifacts in bone SPECT of the pelvis.

OBJECTIVE: Bladder-filling reconstruction artifacts have a detrimental effect on the image quality of pelvic bone single photon emission computed tomography (SPECT). Using a simple protocol consisting of forced diuresis coupled with intravenous (IV) hydration, this study was undertaken to obtain an artifact-free pelvic SPECT after discarding the residual urinary activity. METHODS: Thirty patients were enrolled. In group I, pelvic SPECT was performed directly after normal void, whereas in group II, SPECT was preceded by IV injection of 0.5 mg/kg furosemide (maximum 40 mg) coupled with IV infusion of 500 cc of physiologic saline. Bladder-filling reconstruction artifacts were analyzed in group I patients, who had their images reconstructed using both filtered backprojection and iterative algorithms, both qualitatively and quantitatively by means of regions of interest (ROIs) drawn around the artifact-bearing bone areas as well as the corresponding contralateral sites. For group II patients, besides visual analysis, ROIs were placed over the sites corresponding to those of the group I patients. In every patient, total counts of each ROI were normalized to a reference ROI placed over the sacrum, and a ratio was created. RESULTS: Using filtered backprojection, two forms of artifacts were identified in group I patients: first, a streak pattern that extended to the sacro-iliac joint in nine (60%) patients, the hip joint in five (33%), the superior pubic rami in four (27%), the sacrum in three (20%), and the ischium in one (6%); second, a count loss subtype which extended to the hip joints in nine (60%) patients. Corresponding values after iterative reconstruction were two (13%) for the sacro-iliac joint, three (20%) for the hip joint, one (6%) for the superior pubic ramus, and one (6%) for the sacrum. In five (33%) patients, residual count loss artifacts were still identifiable after iterative reconstruction. However in group II, no such effects were observed because the bladder activity reached near background level in 14 (93%) of 15 patients after three successive voids with a 3.5-fold decrease in the mean value of total bladder count in comparison with group I patients. A statistically significant difference was found between artifact- and non-artifact-harboring ROIs in group I whichever the method used for reconstruction, whereas the values of right and left hemi-pelvis ROIs/sacrum in group II were almost identical. CONCLUSIONS: Forced diuresis coupled with parenteral hydration facilitates the acquisition of an artifact-free pelvic SPECT. Especially for clinical questions that focus on femoral heads and pubic bones, applying the aforementioned protocol may improve the diagnostic accuracy of pelvic bone SPECT

Initial report of PET/CT-guided radiofrequency ablation of liver metastases.

Computed tomography (CT) and ultrasonography (US) are commonly employed to guide positioning of radiofrequency electrodes within target tumors. However, this technique cannot be used when the tumor is detectable only by positron emission tomography (PET). In such cases, even the use of intraprocedural coregistered PET/CT will not prevent malpositioning of the electrode tip relative to a lesion visualized only on PET as a result of patient breathing and organ shifts during CT-guided electrode placement. The present report describes a single case of successful targeting and complete ablation of a lesion invisible on CT and US with the use of a method to visualize electrode tip positioning by PET

Quantification of dose nonuniformities by voxel-based dosimetry in patients receiving 90Y-ibritumomab-tiuxetan.

OBJECTIVE: To assess the impact of nonuniform dose distribution within lesions and tumor-involved organs of patients receiving Zevalin, and to discuss possible implications of equivalent uniform biological effective doses (EU-BED) on treatment efficacy and toxicity. MATLAB? -based software for voxel-based dosimetry was adopted for this purpose. METHODS: Eleven lesions from seven patients with either indolent or aggressive non-Hodgkin lymphoma were analyzed, along with four organs with disease. Absorbed doses were estimated by a direct integration of single-voxel kinetic data from serial tomographic images. After proper corrections, differential BED distributions and surviving cell fractions were estimated, allowing for the calculation of EU-BED. To quantify dose uniformity in each target area, a heterogeneity index was defined. RESULTS: Average doses were below those prescribed by conventional radiotherapy to eradicate lymphoma lesions. Dose heterogeneity and effect on tumor control varied among lesions, with no apparent relation to tumor mass. Although radiation doses to involved organs were safe, unexpected liver toxicity occurred in one patient who presented with a pattern of diffuse infiltration. CONCLUSION: Voxel-based dosimetry and radiobiologic modeling can be successfully applied to lesions and tumor-involved organs, representing a methodological advance over estimation of mean absorbed doses. However, effects on tumor control and organ toxicity still cannot be easily predicted