Vania Altrinetti

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

Purpose18F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on 18F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of 18F-dopa PET/CT in NB and compare its diagnostic value with that of 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3–4 NB.MethodsWe prospectively evaluated 28 paired 123I-MIBG and 18F-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.ResultsNB localizations were confirmed in 17 of 19 patients. 18F-Dopa PET/CT and 123I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, 18F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while 123I-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 18F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, 18F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas 123I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found.ConclusionIn our NB population 18F-dopa PET/CT displayed higher overall accuracy than 123I-MIBG scintigraphy. Consequently, we suggest 18F-dopa PET/CT as a new opportunity for NB assessment.

Pharmacokinetics of Der p 2 Allergen and Derived Monomeric Allergoid in Allergic Volunteers

Background: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers. Methods: Purified Der p 2 and its monomeric allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography. Results: The local pharmacokinetics did not differ between allergen and allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1–2 h. Both the allergen and the allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the allergoid, but not the allergen, was absorbed as an intact molecule. Conclusions: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the allergoid in the mechanism of action of sublingual immunotherapy remains to be defined.

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.

Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival.

Introduction No parameters predicting recurrence are available for high-risk differentiated thyroid cancer (DTC) patients, and 2-year-follow-up is required to modify the initial prognostic classification. High thyroglobulin (Tg) levels before 131I-remnant-ablation, during L-thyroxine-withdrawal (ablation-Tg) have undetermined predictive/prognostic significance in low-risk DTC patients. Our study aimed to assess the positive predictive value (PPV) of ablation-Tg in high-risk DTC patients and to evaluate whether high ablation-Tg levels were associated with progression-free-survival (PFS) and overall survival (OS). Patients and Methods We selected 243 high-risk DTC patients. All patients underwent total thyroidectomy and 131I-remnant-ablation (initial therapy). Clinical data obtained during a median 5-year follow-up were used to assess the response and outcome. The association between disease persistence/recurrence after initial therapy, ablation-Tg, and other risk-factors (T, N, G, histology, and MACIS score) was evaluated through univariate and multivariate analyses, as was the association between PFS, OS ablation-Tg, and other risk factors. Results Ablation-Tg of 50 &mgr;g/L or greater displayed the highest PPV(97%) for disease persistence. In the univariate analysis, high levels of ablation-Tg were confirmed in patients with persistent disease after initial therapy: the higher the odds ratios, the higher the ablation-Tg levels. On multivariate analysis, ablation-Tg was the best predictive factor, especially on comparing patients with ablation-Tg levels of 50 &mgr;g/L or greater and those with ablation-Tg less than 2 &mgr;g/L (adjusted OR, 818). In a multivariate Cox model, ablation-Tg was the factor most closely associated with PFS (HR, 65.9). The prognostic value of ablation-Tg was confirmed by the overall-survival curves and adjusted risk estimates (adjusted HR = 26.7). Conclusions Ablation-Tg levels of 50 &mgr;g/L or greater are a valuable initial predictor of disease persistence/recurrence in high-risk DTC patients. A significant association emerged between high ablation-Tg levels of 50 &mgr;g/L or greater and both progression-free survival (PFS) and overall survival (OS).

Detection of metastatic bone lesions in breast cancer patients: Fused 18F-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.

Pharmacokinetics of radiolabelled Par j 1 administered intranasally to allergic and healthy subjects

Background Local nasal immunotherapy is accepted as an alternative to the injection route for allergic rhinitis. Despite this, little is known about the kinetics of the allergen after nasal delivery in allergic subjects.

18F-FDG PET/CT is a prognostic biomarker in patients affected by bone metastases from breast cancer in comparison with 18F-NaF PET/CT

AIM To compare 18F-FDG PET/CT and 18F-NaF PET/CT with respect to disease prognostication and outcome in patients affected by bone metastases from breast cancer (BC). PATIENTS, METHODS We retrospectively investigated 32 women with BC and documented bone metastases. Semi-quantitative parameters were applied to 18F-FDG PET/CT and 18F-Na PET/CT in order to evaluate disease extent and tumour metabolism. We used time-to-event analyses (Kaplan Meier and COX proportional hazard methods) to estimate progression-free (PFS) and overall survival (OS) in order to assess the independent prognostic value of 18F-FDG PET/CT and 18F-Na PET/CT. RESULTS The sensitivity of 18F-NaF PET/CT (100%) was higher (p < 0.05) than that of 18F-FDG PET/CT (72% and 72%). None of the 18F-FDG PET/CT-negative patients showed disease progression at the end of follow-up. After adjustment for age, Ki-67 levels, presence of visceral metastases, hormone therapy, duration of bone disease and response to first-line therapy, only 18F-FDG SUV mean [HR 15.7, 95% confidence interval (CI) 1.15-214.5] and 18F-FDG whole-body bone metabolic burden (WB-B-MB) (HR 16.9; 95%CI 1.87-152.2) were independently and significantly associated with OS. None of the 18F-NaF PET/CT parameters were associated with OS. None of the conventional clinical prognostic parameters remained significantly associated with OS after the inclusion of PET/CT parameters in the model. CONCLUSION 18F-FDG PET/CT is independently associated with OS in BC patients with bone metastases and its prognostic impact seems to be higher than conventional clinical and biological prognostic factors. Although 18F-NaF PET/CT has a higher diagnostic sensitivity than 18F-FDG PET/CT, it is not independently associated with OS.

Allergen Biodistribution in Humans

Specific immunotherapy performed by noninjectable (oral, nasal or oromucosal) routes was mostly developed in the last 20 years with the main aim to avoid side effects that occasionally occur in the course of injectable immunotherapy. Although evidence of its clinical efficacy has been provided some pharmacokinetics aspects are still to be elucidated. In this review we discuss experimental findings of mucosal processing, biodistribution in healthy or allergic humans of 123I-labelled major allergen of Parietaria judaica (the most important cause of seasonal allergy in the Mediterranean area) administered by sublingual or nasal routes. The results available to date show that most allergen administered by mucosal route is absorbed via the gastrointestinal tract; however, a proportion is retained at the mucosal level for a relatively long time. These data are potentially useful to improve immunotherapy treatment protocols by noninjectable routes.

The incidental discovery of follicular thyroid cancer with in-111 pentetreotide scintigraphy in a patient with carcinoid tumor of the lung.

Although scintigraphy with the somatostatin receptor agent In-111 pentetreotide is most useful in patients with amine precursor uptake and decarboxylation-derived tumors, several reports note the tumor-targeting potential of this radiopharmaceutical in other types of cancers as well. The authors describe a 38-year-old woman with carcinoid tumor of the lung in whom scintigraphy with labeled pentetreotide was positive in the known lung tumor and incidentally revealed uptake in a thyroid nodule. Although the serum calcitonin level was normal, fine-needle cytology of the thyroid nodule was consistent with follicular cancer. The patient underwent resection of the lower lobe of the left lung and total thyroidectomy, which confirmed a follicular cancer in the right thyroid lobe.

Comparisons between glucose analogue 2-deoxy-2-(18F)fluoro-D-glucose and 18F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM To compare 2-deoxy-2-((18)F)fluoro-D-glucose((18)F-FDG) and (18)F-sodium ((18)F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases. METHODS A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent (18)F-FDG and (18)F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youdens index. McNemars χ(2) test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding (18)F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to (18)F-NaF PET/CT findings. RESULTS The two imaging methods of (18)F-FDG and (18)F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemars χ(2) = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemars χ(2) = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, (18)F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); (18)F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). (18)F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at (18)F-FDG PET/CT. CONCLUSION (18)F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of (18)F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of (18)F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative (18)F-FDG PET and conventional imaging).