Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study.

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

Longitudinal analysis of atherosclerotic plaques evolution: an 18F-NaF PET/CT study.

PURPOSE: 18F-NaF-PET/CT can detect mineral metabolism within atherosclerotic plaques. To ascertain whether their 18F-NaF uptake purports progression, this index was compared with subsequent morphologic evolution. METHODS: 71 patients underwent two consecutive 18F-NaF-PET/CTs (PET1/PET2). In PET1, non-calcified 18F-NaF hot spots were identified in the abdominal aorta. Their mean/max HU was compared with those of a non-calcified control region (CR) and with corresponding areas in PET2. A target-to-background ratio (TBR), mean density (HU), and calcium score (CS) were calculated on calcified atherosclerotic plaques in PET1 and compared with those in PET2. A VOI including the entire abdominal aorta was drawn; mean TBR and total CS were calculated on PET1 and compared with those PET2. RESULTS: Hot spots in PET1 (N = 179) had a greater HU than CR (48 ± 8 vs 37 ± 9, P < .01). Mean hot spots HU increased to 59 ± 12 in PET2 (P < .001). New calcifications appeared at the hot spots site in 73 cases (41%). Baseline atherosclerotic plaque's (N = 375) TBR was proportional to percent HU and CS increase (P < .01 for both). Aortic CS increased (P < .001); the whole-aorta TBR in PET1 correlated with the CS increase between the baseline and the second PET/CT (R = .63, P < .01). CONCLUSIONS: 18F-NaF-PET/CT depicts the early stages of plaques development and tracks their evolution over time.

To Enhance or Not to Enhance? The Role of Contrast Medium 18F-FDG PET/CT in Recurrent Ovarian Carcinomas.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings; however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT; 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

How to better stratify the risk of differentiated thyroid carcinomas: the key role of radioactive iodine therapy, age, and gender.

PURPOSE: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. METHODS: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (ΔC-index = + 5.1%, P < .001). CONCLUSIONS: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

Unstimulated Serum Thyroglobulin Levels after Thyroidectomy and Radioiodine Therapy for Intermediate-Risk Thyroid Cancer Are Not Always a Reliable Marker of Lymph Node Recurrence: Case Report and a Lesson for Clinicians.

Over 50% of patients with papillary thyroid carcinoma (PTC) have cervical lymph-node metastasis on diagnosis, and up to 30% show nodal recurrence after surgery plus radioactive iodine (131I) (RAI) therapy. The combination of ultrasonography (US) and fine-needle aspiration cytology (FNAC) and the measurement of thyroglobulin (Tg) in washout fluid are cornerstones in the diagnosis of nodal metastasis. In the absence of anti-Tg antibodies, unstimulated serum thyroglobulin (Tg) levels are generally a reliable marker of recurrent disease, and 18F-FDG positron emission tomography (PET)/computed tomography (CT) plays an important role in the imaging work-up. We report the case of a 65-year-old man evaluated for a large multinodular goitre which caused compressive symptoms; the dominant nodule in the left lobe presented suspicious features on US. Thyroid function showed subclinical hypothyroidism, calcitonin was normal, serum thyroglobulin levels were low, and anti-thyroid antibodies were absent. The prevalent left nodule showed an intense uptake on 18F-FDG PET/CT but proved benign at FNAC. On the basis of the suspicious clinical and imaging features, total thyroidectomy was performed. Histology revealed a tall-cell variant of PTC with scattered expression of Tg and diffuse high expression of cytokeratin (CK) 19; RAI therapy was performed. Within 6 years of surgery, left laterocervical lymph-node recurrence was twice detected (first at levels II and III, then at levels IV and VI) by US and 18F-FDG-PET/CT and was confirmed by FNAC. Tg levels in the washout fluid proved clearly diagnostic of metastasis only in the second, larger, recurrence, whereas serum Tg levels (in the absence of anti-Tg antibodies) always remained undetectable on L-thyroxine therapy. Surgery was performed on both recurrences, and histology confirmed lymph-node metastasis of PTC. Immunohistochemical expression of Tg and CK 19 was similar to that of the primary tumour. No further relapses have occurred to date. Posttherapy (surgery and RAI) unstimulated serum Tg levels may not be a reliable marker of nodal recurrence in patients with differentiated thyroid cancer (DTC) that produces low amounts of Tg.

The Additional Value of 18F-FDG PET and MRI in Patients with Glioma: A Review of the Literature from 2015 to 2020.

AIM: Beyond brain computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) hold paramount importance in neuro-oncology. The aim of this narrative review is to discuss the literature from 2015 to 2020, showing advantages or complementary information of fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging to the anatomical and functional data offered by MRI in patients with glioma. METHODS: A comprehensive Pubmed/MEDLINE literature search was performed to retrieve original studies, with a minimum of 10 glioma patients, published from 2015 until the end of April 2020, on the use of 18F-FDG PET in conjunction with MRI. RESULTS: Twenty-two articles were selected. Combined use of the two modalities improves the accuracy in predicting prognosis, planning treatments, and evaluating recurrence. CONCLUSION: According to the recent literature, 18F-FDG PET provides different and complementary information to MRI and may enhance performance in the whole management of gliomas. Therefore, integrated PET/MRI may be particularly useful in gliomas, since it could provide accurate morphological and metabolic information in one-shoot examination and improve the diagnostic value compared to each of procedures.

Role of 18F-Choline Positron Emission Tomography/Computed Tomography to Detect Structural Relapse in High-Risk Differentiated Thyroid Cancer Patients.

BACKGROUND: This study aimed to evaluate the role of 18F-choline (18F-FCH) positron emission tomography (PET)/computed tomography (CT) in high-risk differentiated thyroid cancer (DTC) patients with suspected relapse. It also compared 18F-FCH-PET/CT results with those of fludeoxyglucose (18F-FDG)-PET/CT and evaluated the additional diagnostic value and clinical impact of the combined use of these two tracers. Finally, it assessed the association between the clinical, biochemical, and histological parameters and 18F-FCH-PET/CT and 18F-FDG-PET/CT results. METHODS: The study prospectively enrolled high-risk DTC patients treated with thyroidectomy and radioactive iodine therapy and presenting high/increasing thyroglobulin levels under thyrotropin suppression, negative/inconclusive neck ultrasound, and negative 131I whole-body scan. All patients underwent 18F-FDG-PET/CT and 18F-FCH-PET/CT within 30 days of each other. Experienced nuclear medicine physicians examined the images of both procedures, and an integrated analysis of the two PET/CT modalities was also conducted. For each modality, a patient-based analysis (PBA) and lesion-based-analysis (LBA) was performed. On PBA, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated. On LBA, only sensitivity was calculated. The standard of reference was based on clinical, imaging, and histological data. RESULTS: Twenty-five high-risk DTC patients were included; DTC relapse/persistence was confirmed in 23 patients. On PBA, 18F-FDG-PET/CT, 18F-FCH-PET/CT, and the integrated evaluation of the two imaging modalities showed the following rates: sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 69.6%, 100%, 22.2%, 100%, and 72% versus 56.5%, 100%, 16.7%, 100%, and 60% versus 82.6%, 100%, 33.3%, 100%, and 84%, respectively. When compared with 18F-FDG-PET/CT, the integrated analysis of these two imaging procedures changed the clinical management in 4/23 (17%) patients. On LBA, the sensitivity rates of 18F-FDG-PET/CT, 18F-FCH-PET/CT, and the combined evaluation of the two modalities were 58.7%, 38.1%, and 66.7%, respectively; when only lymph node involvement was considered, the rates were 56.3%, 53.1%, and 68.8%, respectively. Serum thyroglobulin doubling time (Tg-DT) <12 months was significantly associated with positive 18F-FCH-PET/CT. A trend toward a significant association was also found between positive 18F-FDG-PET/CT and both Tg-DT <12 months and DTC aggressive subtypes. CONCLUSION: 18F-FCH-PET/CT may add important information during the follow-up of high-risk DTC patients. 18F-FCH-PET/CT may be considered a useful complementary tool in patients affected by non-aggressive DTC subtypes, with Tg-DT <12 months, high risk of lymph node spreading, and negative or doubtful 18F-FDG-PET/CT.

Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: possible theranostic implications.

BACKGROUND: The aim of the present study is to evaluate the kinetics and dosimetry of 64CuCl2 in human prostate cancer (PCa) lesions. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external beam radiation therapy. All patients underwent 64CuCl2-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each 64CuCl2 avid PCa lesion with a diameter > 1 cm on mpMRI in each patient. Time-activity curves for all lesions were obtained. The effective and biological half-life and the standard uptake values (SUVs) were calculated. Tumour/background ratio (TBR) curves as a function of time were considered. Finally, the absorbed dose per lesion was estimated. RESULTS: The mean effective half-life of 64CuCl2 calculated in the lymph nodes (10.2 ± 1.7 h) was significantly higher than in local relapses (8.8 ± 1.1 h) and similar to that seen in bone metastases (9.0 ± 0.4 h). The mean 64CuCl2 SUVmax calculated 1 h after tracer injection was significantly higher in the lymph nodes (6.8 ± 4.3) and bone metastases (6.8 ± 2.9) than in local relapses (4.7 ± 2.4). TBR mean curve of 64CuCl2 revealed that the calculated TBRmax value was 5.0, 7.0, and 6.2 in local relapse and lymph node and bone metastases, respectively, and it was achieved about 1 h after 64CuCl2 injection. The mean absorbed dose of the PCa lesions per administrated activity was 6.00E-2 ± 4.74E-2mGy/MBq. Indeed, for an administered activity of 3.7 GBq, the mean dose absorbed by the lesion would be 0.22 Gy. CONCLUSIONS: Dosimetry showed that the dose absorbed by PCa recurrences/metastases per administrated activity was low. The dosimetric study performed does not take into account the possible therapeutic effect of the Auger electrons. Clinical trials are needed to evaluate 64Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.

Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?

PURPOSE: Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS: After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS: We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS: Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.

64CuCl2 PET/CT in Prostate Cancer Relapse.

Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of 64CuCl2 in humans and to assess the ability of 64CuCl2 PET/CT to detect prostate cancer (PCa) recurrence in patients with biochemical relapse. Methods: We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent 64CuCl2 PET/CT, 18F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of 64CuCl2 were evaluated. Results: From a dosimetric point of view, an administered dose of 200 MBq for 64CuCl2 translated into a 5.7-mSv effective dose. Unlike 18F-choline, 64CuCl2 was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum 64CuCl2 uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, 64CuCl2 PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of 18F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of 64CuCl2 PET/CT and 18F-choline PET/CT was statistically significant (P < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, 64CuCl2 PET/CT had a higher DR than 18F-choline PET/CT in patients with a PSA of less than 1 ng/mL. Conclusion: The biodistribution of 64CuCl2 is more suitable than that of 18F-choline for exploring the pelvis and prostatic bed. The 64CuCl2 effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, 64CuCl2 PET/CT shows a significantly higher DR than 18F-choline PET/CT.

Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET.

PURPOSE: The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with 18F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). METHODS: We retrospectively analyzed 26 children with histologically proven treatment naïve low and high grade DAT who underwent ASL and DWI performed within 2 weeks of 18F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with 18F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. RESULTS: A significant correlation was demonstrated between rCBF max, rADC min, and 18F-DOPA PET data (p < 0.001). Significant differences in terms of rCBF max, rADC min, and 18F-DOPA uptake were found between low- and high-grade DAT (p ≤ 0.001). ROC analysis and DFA demonstrated that T/S and T/N values were the best parameters for predicting tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic tools correlated with PFS (p ≤ 0.001); however, on multivariate analysis, only 18F-DOPA uptake remained significantly associated with outcome (p ≤ 0.03), while a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination of MRI and PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p < 0.001). CONCLUSIONS: DWI, ASL and 18F-DOPA PET provide useful complementary information for pediatric DAT grading. 18F-DOPA uptake better correlates with PFS prediction. Combining MRI and PET data provides the highest predictive power for prognosticating tumor progression suggesting a synergistic role of these diagnostic tools.

Differentiated Thyroid Cancer lymph-node relapse. Role of adjuvant radioactive iodine therapy after lymphadenectomy.

PURPOSE: Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy. METHODS: We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1-3 months after lymphadenectomy and of other risk factors. RESULTS: We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31-59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on <1 ng/ml. Multivariate models showed that age, Tg-on (≥1 vs. < 1 ng/ml, HR: 18.2, 95% CI: 5.09-64.8, p = 0.001) and RAI (Yes vs. No, HR: 0.36,95%CI: 0.15-0. 9, p = 0.02) remained the only independent factors associated with PFS, but only age and Tg-on remained significantly associated with OS (HR: 8.31, 95%CI:1.56-44.3, p = 0.01). Nonetheless, patients treated with RAI showed a lower risk of mortality (HR: 0.34, 95%CI: 0.1-1.15 p = 0.08) than untreated patients. CONCLUSIONS: RAI after lymphadenectomy for DTC relapse is significantly associated with better PFS only in patients with Tg-on ≥1 ng/ml.

18F-DOPA Uptake of Developmental Venous Anomalies in Children With Brain Tumors.

We report the finding of increased F-3,4-dihydroxyphenylalanine uptake of the brain parenchyma adjacent to developmental venous anomalies, incidentally discovered in 3 pediatric patients with diffusely infiltrating gliomas. One patient presented 3 developmental venous anomalies located distant from the tumor, whereas in the remaining 2 patients, the vascular anomalies were inside the tumoral area mimicking a focal area of increased tumor metabolism. In the setting of brain tumor imaging, focal increased F-3,4-dihydroxyphenylalanine uptake should be carefully interpreted in light of MRI findings, and nuclear medicine physicians should be aware of any incidental minor vascular abnormality for proper interpretation of PET data.

Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk.

AIM: To investigating the relationship between thoracic and cardiac (18)F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors. METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta. RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively). CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients' risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.

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.

¹8F-FDG uptake as a prognostic variable in primary differentiated thyroid cancer incidentally detected by PET/CT: a multicentre study.

PURPOSE: Our aim was to investigate the association between (18)F-fluorodeoxyglucose (FDG) uptake and event-free survival in patients in whom a differentiated thyroid cancer (DTC) was detected by (18)F-FDG positron emission tomography (PET)/CT. METHODS: Among 884 focal (18)F-FDG PET thyroid incidentalomas referred to our 4 Nuclear Medicine Departments, we investigated 54 patients in whom a DTC was confirmed and a clinical follow-up was available. The ratio between maximum standardized uptake value (SUVmax) of DTC and SUVmean of the liver (SUV ratio) was recorded for each scan. All patients underwent total thyroidectomy and (131)I remnant ablation. After a median follow-up of 39 months we assessed the outcome. The association between disease persistence/progression, (18)F-FDG uptake and other risk factors (T, N, M and histological subtype) was evaluated through univariate and multivariate analyses. RESULTS: Of the 54 patients, 39 achieved complete remission. The remaining 15 showed persistence/progression of disease. High (18)F-FDG uptake, i.e. SUV ratio ≥3, showed a low positive predictive value (48 %). Low (18)F-FDG uptake (SUV ratio < 3) displayed a high negative predictive value (93 %). The median of SUV ratios in T1-T2 (2.2), in M0 (2.7) and in non-virulent subtypes (2.7) were significantly lower (p < 0.03) than in T3-T4 (5.0), M1 (7.3) and virulent subtypes (6.0). Kaplan-Maier analysis showed a significant association between high (18)F-FDG uptake and disease persistence/progression (p = 0.001). When we adjusted risk estimates by using a multivariate Cox model, only T (p = 0.05) remained independently associated with disease persistence/progression. CONCLUSION: An intense (18)F-FDG uptake of the primary DTC is associated with persistence/progression of disease. However, when all other prognostic factors have been taken into account, (18)F-FDG uptake does not add further prognostic information.

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.

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.

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 µg/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 µg/L or greater and those with ablation-Tg less than 2 µg/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 µg/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 µg/L or greater and both progression-free survival (PFS) and overall survival (OS).

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.