¹8F-NaF Uptake by Atherosclerotic Plaque on PET/CT Imaging: Inverse Correlation Between Calcification Density and Mineral Metabolic Activity.

UNLABELLED: Several studies have highlighted the role of vascular (18)F-NaF uptake as a marker of ongoing calcium deposition. However, accumulation of (18)F-NaF is often inconsistent with localization of arterial plaque. Calcification activity and thus (18)F-NaF uptake might prevail in the earlier plaque stages. To test this hypothesis, we evaluated (18)F-NaF uptake in plaque of 3 different densities, using density as a marker of calcification progression. We also tested whether attenuation-weighted image reconstruction affects (18)F-NaF uptake in the different plaque stages. METHODS: Sixty-four oncologic patients (14 men and 50 women; mean age, 65.3 ± 8.2 y; range, 26-81 y) underwent (18)F-NaF PET/CT. A volume of interest was drawn on each plaque within the infrarenal aorta to assess mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque was then categorized as light (<210 HU), medium (211-510 HU), or heavy (>510 HU). Standardized uptake value was normalized for blood (18)F-NaF activity to obtain the plaque target-to-background ratio (TBR). During this process, several focal, noncalcified areas of (18)F-NaF were identified (hot spots). The TBR of the hot spots was computed after isocontour thresholding. The TBR of a noncalcified control region was also calculated. In 35 patients, the TBR of non-attenuation-corrected images was calculated. RESULTS: The average TBR was highest in light plaque (2.21 ± 0.88), significantly lower in medium plaque (1.59 ± 0.63, P < 0.001), and lower still in heavy plaque (1.14 ± 0.37, P < 0.0001 with respect to both light and medium plaque). The TBR of the control region was not significantly different from that of heavy plaque but was significantly lower than that of light and medium plaque (P < 0.01). Hot spots had the highest absolute TBR (3.89 ± 1.87, P < 0.0001 vs. light plaque). TBRs originating from non-attenuation-corrected images did not significantly differ from those originating from attenuation-corrected images. CONCLUSION: Our results support the concept that (18)F-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanisms are the main determinants of calcium presence, but that retention of (18)F-NaF progressively decreases with increasing calcium deposition in the arterial wall. Our data suggest that non-attenuation-corrected reconstruction does not significantly affect evaluation of plaque of any thickness.

Giant cell arteritis: a systematic review of the qualitative and semiquantitative methods to assess vasculitis with 18F-fluorodeoxyglucose positron emission tomography.

Giant cell arteritis (GCA) is the most common vasculitis affecting medium and large vessels. It shows a close clinical association with polymyalgia rheumatica (PMR), a musculoskeletal inflammatory disorder, which is clinically characterized by girdles pain and stiffness. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an effective tool for the diagnosis, grading, and follow-up of patients affected by GCA involving the aorta and its proximal branches, but the lack of a standardized method for the assessment of vascular inflammation remains a critical issue, potentially leading to misclassification. In our systematic review, including 19 original articles for a total of 442 GCA patients (with or without PMR symptoms) and 535 healthy controls, we described the different qualitative, semiquantitative and combined methods that have been proposed throughout the literature for assessing the presence and grading the severity of GCA-related vascular inflammation on 18F-FDG PET scans, focusing on the diagnostic performance and examining their respective advantages and limitations. The majority of the included studies adopted qualitative methods of PET image analysis, which are less sensitive but more specific than semiquantitative ones. Among the semiquantitative approaches, the aortic-to-blood pool uptake ratio of the aortic arch seems to be the most accurate method.

Prognostic value of ¹8F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma.

PURPOSE: The aim of this study was to investigate the relationship between (123)I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new (18)F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS). METHODS: We analysed 24 NB patients who had undergone (123)I-MIBG and (18)F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of (123)I-MIBG and (18)F-DOPA PET/CT scans. RESULTS: The (123)I-MIBG and (18)F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14 months (range 6-82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95% confidence interval (CI) 2.7-109] in NB patients with (123)I-MIBG score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95% CI 2.4-574) in those with (18)F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for (123)I-MIBG and (18)F-DOPA WBMB, respectively). CONCLUSION: Our results confirm the good agreement between (18)F-DOPA PET/CT and (123)I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, (123)I-MIBG scan and (18)F-DOPA PET/CT scores were independently and significantly associated with disease progression.

Bone and lymph node metastases from neuroblastoma detected by 18F-DOPA-PET/CT and confirmed by posttherapy 131I-MIBG but negative on diagnostic 123I-MIBG scan.

We report the case of a 6-year-old child with stage 4 neuroblastoma, previously treated with chemotherapy, which relapsed in the right mandibular branch, right submandibular lymph nodes, and bone marrow. These sites of recurrence were detected on diagnostic (123)I-MIBG and confirmed by (18)F-DOPA-PET/CT, which revealed the following 2 additional sites of disease: in the skull base and the left supraclavicular lymph nodes. The patient was scheduled for radioiodine therapy and received a total dose of 7400 MBq (200 mCi) of (131)I-MIBG. The whole-body scan, acquired 72 hours later, revealed all sites of disease detected by (18)F-DOPA-PET/CT, including those negative on (123)I-MIBG scan.

Divergent determinants of 18F-NaF uptake and visible calcium deposition in large arteries: relationship with Framingham risk score.

To compare regional vascular distribution and biological determinants of visible calcium load, as assessed by computed tomography, as well as of molecular calcium deposition as assessed by (18)F-NaF positron emission tomography. Eighty oncologic patients undergoing (18)F-NaF PET/CT scan were included in the study. Cardiovascular-risk stratification was performed according to a simplified version of the Framingham model [including age, diabetes, smoking, systolic blood pressure and body mass index (BMI)]. Arterial (18)F-NaF uptake was measured by drawing regions of interest comprising the arteries on each slice of the transaxial PET/CT and normalized to blood (18)F-NaF activity to obtain the arterial target-to-background ratio (TBR). The degree of arterial calcification (AC) was measured using a software program providing Agatston-like scores. Differences in mean values and regression analysis were tested. Predictors of AC and TBR were evaluated by univariate and multivariate analysis. p value of 0.05 was considered statistically significant. No correlation was documented between regional calcium load and regional TBR in any of the studied arterial segments. Visible calcium deposition was found to be dependent upon age while it was not influenced by all the remaining determinants of cardiovascular risk. By contrast, (18)F-NaF uptake was significantly correlated with all descriptors of cardiovascular risk, with the exception of BMI. Vascular (18)F-NaF uptake displays a different regional distribution, as well as different biological predictors, when compared to macroscopic AC. The tight dependency of tracer retention upon ongoing biological determinants of vascular damage suggests that this tool might provide an unexplored window on plaque pathophysiology.

18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR.

AIM: Role of 18F-DOPA PET/CT in neuroblastoma (NB) compared with CT/MR. MATERIALS AND METHODS: In all, 21 patients (M:F = 14:7; mean age, 7.4 years) affected by advanced stage NB (III-IV) were prospectively enrolled. Overall, 37 paired 18F-DOPA PET and CT/MR scans were performed, and for each, we identified site and number of lesions. Standard of reference was based on a multidisciplinary assessment, including 123I-MIBG, selective biopsy, and clinical-instrumental monitoring. Both scan-based and a lesion-based analysis was performed, and for each modality, we calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: On the scan-based analysis, 18F-DOPA PET and CT/MR showed the following rates: sensitivity, specificity, NPV, PPV, and accuracy were 100%, 92.3%, 100%, 96%, and 97.3% versus 91.7%, 61.5%, 80%, 81.5%, and 81.1%, respectively (P = 0.014). Overall 179 findings were reported at imaging, of which 139 (77.7%) resulted true sites of disease at final outcome. On the lesion-based analysis, the 2 imaging modalities showed the following sensitivity, specificity, NPV, PPV, and accuracy rates: 90.6%, 90%, 73.5%, 96.9%, and 90.5% versus 47.5%, 27.5%, 13.1%, 69.5%, and 43% (P < 0.00001). CONCLUSIONS: In our study, 18F-DOPA PET/CT results more accurate than CT/MR in advanced stage NB therefore should be taken into consideration for the diagnostic workup of these patients.

Detection of metastatic bone lesions in breast cancer patients: fused (18)F-Fluoride-PET/MDCT has higher accuracy than MDCT. Preliminary experience.

PURPOSE: So far, no studies comparing (18)F-Fluoride-PET/CT and MDCT for the detection of bone metastases are available. We compared the accuracy of (18)F-Fluoride-PET/CT (MDCT: 3.75 mm thickness-image-reconstruction), whole-body Multi-Detector-CT (MDCT: 1.25 mm thickness-image-reconstruction) and (18)F-Fluoride-PET/MDCT (MDCT: 1.25 mm thickness-image-reconstruction) in identifying bone metastases in breast cancer patients. METHODS: We studied 39 breast cancer patients for bone metastases. Imaging was performed on an integrated PET/MDCT-system; CT images were reconstructed at 3.75 mm and 1.25 mm thickness. Two nuclear medicine physicians and one radiologist interpreted blindly (18)F-Fluoride-PET/CT, (18)F-Fluoride-PET/MDCT and MDCT. MDCT at 12 months served as the standard of reference. RESULTS: Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference. (18)F-Fluoride-PET/CT detected 491 bone metastases, 114 (23%) of which displayed no clear morphological changes on MDCT, whereas MDCT detected 416 bone metastases, 39 (9.3%) of which showed no (18)F-Fluoride-PET uptake. Overall sensitivity and specificity were: 91% and 91%, respectively, for (18)F-Fluoride-PET/CT, and 77% and 93% for MDCT. The integrated assessment of (18)F-Fluoride-PET/MDCT yielded sensitivity and specificity values of 98% and 93%, respectively. CONCLUSIONS: (18)F-Fluoride-PET/MDCT has higher diagnostic accuracy than (18)F-Fluoride-PET/CT and MDCT for the evaluation of bone metastases in breast cancer.

Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study.

PURPOSE: (18)F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on (18)F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of (18)F-dopa PET/CT in NB and compare its diagnostic value with that of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3-4 NB. METHODS: We prospectively evaluated 28 paired (123)I-MIBG and (18)F-dopa PET/CT scans in 19 patients: 4 at the time of the NB diagnosis and 15 when NB relapse was suspected. For both imaging modalities we performed a scan-based and a lesion-based analysis and calculated sensitivity, specificity and accuracy. The standard of reference was based on clinical, imaging and histological data. RESULTS: NB localizations were confirmed in 17 of 19 patients. (18)F-Dopa PET/CT and (123)I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while (123)I-MIBG scanning showed a sensitivity and accuracy of 68 and 64%, respectively (p < 0.05). No significant difference in terms of specificity was found. In 9 of 28 paired scans (32%) PET/CT results influenced the patient management. We identified 156 NB localizations, 141 of which were correctly detected by (18)F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas (123)I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found. CONCLUSION: In our NB population (18)F-dopa PET/CT displayed higher overall accuracy than (123)I-MIBG scintigraphy. Consequently, we suggest (18)F-dopa PET/CT as a new opportunity for NB assessment.

Whither the PET scan? The role of PET imaging in the staging and treatment of breast cancer.

Metabolic imaging may contribute to a better knowledge of the biology of breast cancer and to new drugs development. Positron emission tomography (PET) with the radiolabeled glucose analogue 2- [18F]-fluorodeoxyglucose (18F-FDG) allows quantitative assessment of glucose utilization in tumor tissue. This technique utilizes a class of radioisotopes that decay by emitting a positron. The positron travels a short distance (1 mm) before interacting with an electron in what is called an annihilation reaction. This results in the creation of two high-energy photons that are emitted in opposite directions. The PET scanner detects such annihilation radiations and produces a three-dimensional picture of the distribution of the radiolabeled tracer. 18F-FDG PET has currently a limited role in breast cancer, due to its low sensitivity that makes it not recommended in most of the cases, especially in early disease. Potentially, the most useful application of PET/CT is monitoring the changes in 18F-FDG uptake during chemotherapy in order to detect an early response to treatment. In fact, while morphological changes due to effective chemotherapy are not detectable until late in the course of treatment, metabolic changes generally occur earlier. In this paper, we summarize the current and future applications of PET in the management of breast cancer.

Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study.

PURPOSE: To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). METHODS: Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. RESULTS: As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. CONCLUSION: The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate-precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD.

Skeletal involvement in infants with neuroblastoma a quality control attempt.

AIMS AND BACKGROUND: In 1994, French authors hypothesized that positive skeletal mlBG spots in infants with stage 4 neuroblastoma were not prognostically unfavorable unless associated to abnormal standard X-ray or CT findings. In 1999, the European Infant Neuroblastoma Study adopted this definition, indeed reducing the number of patients candidate to chemotherapy. Such an approach requires high quality scans and standardized procedures. The present study critically reviewed and assessed the quality of mlBG scans performed in Italian patients enrolled in the European Infant Neuroblastoma Study. METHODS: Three independent nuclear medicine specialists reviewed scans of 25 Italian patients enrolled in Trials 99.2, 99.3, and 99.4 of the European Infant Neuroblastoma Study between January 2000 and September 2002. An arbitrary quality score was attributed to each mlBG scintigraphy, ranging from 1 (less than adequate) to 3 (excellent). One radiologist and 2 oncologists reviewed the X-rays and CT scans and correlated the results with clinical assessment. RESULTS: The quality of mlBG scans was rated from good to excellent in 15 of 25 cases, poor in 4, and inadequate for diagnostic evaluation in 6. X-rays confirmed the presence of metastases in 3 of 7 cases with mlBG bone uptake. CT scan confirmed skull metastases in 6 of 9 mlBG-positive cases. Discrepancies in scan interpretation, making trial and stage attribution questionable, were found in 2 patients and are discussed. CONCLUSIONS: The quality of mlBG scans proved to be at least acceptable in most Italian pediatric oncology centers. Efforts should be made to further standardize evaluation of the scans. Additional techniques (99mTc scintigraphy, MRI, SPECT) might be useful to help understand the most complex cases.

Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine.

BACKGROUND: (131)I-metaiodobenzylguanidine ((131)I-MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. Radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow-up, other complications might occur. We describe our experience with second cancers occurring in children treated with (131)I-MIBG and chemotherapy. METHODS: The clinical records of 119 consecutive NB cases treated with (131)I-MIBG at a single institution between 1984 and 2001 were reviewed for the occurrence of a second malignant neoplasm (SMN). RESULTS: Overall, five cases of SMN occurred in the study patients. In particular, two cases of myeloid leukemia, one of angiomatous fibrous histiocytoma, one of malignant schwannoma, and one case of rhabdomyosarcoma were detected. The schwannoma and the rhabdomyosarcoma developed within the residual neuroblastic mass after first-line therapy. CONCLUSIONS: Should (131)I-MIBG treatment become more broadly employed in the therapeutic strategy for neuroblastoma, the risk of second cancer will have to be taken into consideration. The organization of an international registry of subjects treated with (131)I-MIBG might better define the frequency and features of second malignancies following this radiometabolic approach.