Angelina Filice

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

PurposeTo retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels.MethodsIncluded in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis.ResultsAt least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between 18F-DOPA and 18F-FDG PET/CT (p < 0.01) and between 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by 18F-DOPA PET/CT and 18F-FDG PET/CT (p < 0.01 for all the analyses) and by 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%).Conclusion18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour.

Differentiated Thyroid Cancer: A New Perspective with Radiolabeled Somatostatin Analogues for Imaging and Treatment of Patients

BACKGROUND The expression of somatostatin receptors (SSTR) in thyroid cells may offer the possibility to identify metastatic lesions and to select patients for peptide receptor radionuclide therapy (PRRT). We investigated (68)Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) to select patients with progressive differentiated thyroid cancer (DTC) for PRRT as well as treatment response and toxicity in treated patients. METHODS We enrolled 41 patients with progressive radioiodine-negative DTC (24 women and 17 men; mean age=54.3 years, median=59 years, range=19-78 years). In all patients, [(18)F]FDG-PET/CT was performed to determine recurrent disease with enhanced glucose metabolism, and (68)Ga-DOTATOC PET/CT was used to identify SSTR expression. Dosimetric evaluation was performed with (111)In-DOTATOC scintigraphy. Eleven patients were treated with PRRT receiving a fractionated injection of 1.5-3.7 GBq (90)Y-DOTATOC/administration. Serial (68)Ga-DOTATOC PET/CT scans were performed in all treated patients to evaluate treatment response. Parameters provided by (68)Ga-DOTATOC PET/CT were analyzed as potential therapeutic predictors to differentiate responding from nonresponding. In all treated patients, adverse events and toxicity were recorded. RESULTS (68)Ga-DOTATOC PET/CT were positive in 24/41 of radioiodine-negative DTC patients. Based on the high expression of SSTR detected by (68)Ga-DOTATOC PET/CT, 13 patients were suitable for PRRT. Two out of 13 patients were not treated due to the lack of fulfillment of other study inclusion criteria. PRRT induced disease control in 7/11 patients (two partial response and five stabilization) with a duration of response of 3.5-11.5 months. Objective response was associated with symptoms relief. Functional volume (FV) over time obtained by PET/CT was the only parameter demonstrating a significant difference between lesions responding and nonresponding to PRRT (p=0.001). Main PRRT adverse events were nausea, asthenia, and transient hematologic toxicity. One patient experienced permanent renal toxicity. CONCLUSIONS In our series, SSTR imaging provided positive results in more than half of the cases with radioiodine-negative DTC, and about one third of patients were eligible for PRRT. (68)Ga-DOTATOC PET/CT seems a reliable tool both for patient selection and evaluation of treatment response. In our experience, FV determination over time seems to represent a reliable parameter to determine tumor response to PRRT, although further investigations are needed to better define its role.

Radiolabeled Somatostatin Analogues Therapy in Advanced Neuroendocrine Tumors: A Single Centre Experience

The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33–83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using 68Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq (90Y-DOTATOC/DOTATATE) or 6.0 GBq (177Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.

PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids

Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.

Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid

Purpose The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. Methods Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUVmax, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUVT/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUVT/S), the ratio between SUVmax of 68Ga-DOTA-peptides PET/CT, and the SUVmax of 18F-FDG PET/CT (SUVmax ratio). Histology was used as reference standard. Results Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUVmax ratio was the most accurate semiquantitative index in identifying TC. Conclusions Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUVmax ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

The unbearable lightness of health science reporting: a week examining Italian print media.

Background Although being an important source of science news information to the public, print news media have often been criticized in their credibility. Health-related content of press media articles has been examined by many studies underlining that information about benefits, risks and costs are often incomplete or inadequate and financial conflicts of interest are rarely reported. However, these studies have focused their analysis on very selected science articles. The present research aimed at adopting a wider explorative approach, by analysing all types of health science information appearing on the Italian national press in one-week period. Moreover, we attempted to score the balance of the articles. Methodology/Principal Findings We collected 146 health science communication articles defined as articles aiming at improving the readers knowledge on health from a scientific perspective. Articles were evaluated by 3 independent physicians with respect to different divulgation parameters: benefits, costs, risks, sources of information, disclosure of financial conflicts of interest and balance. Balance was evaluated with regard to exaggerated or non correct claims. The selected articles appeared on 41 Italian national daily newspapers and 41 weekly magazines, representing 89% of national circulation copies: 97 articles (66%) covered common medical treatments or basic scientific research and 49 (34%) were about new medical treatments, procedures, tests or products. We found that only 6/49 (12%) articles on new treatments, procedures, tests or products mentioned costs or risks to patients. Moreover, benefits were always maximized and in 16/49 cases (33%) they were presented in relative rather than absolute terms. The majority of stories (133/146, 91%) did not report any financial conflict of interest. Among these, 15 were shown to underreport them (15/146, 9.5%), as we demonstrated that conflicts of interest did actually exist. Unbalanced articles were 27/146 (18%). Specifically, the probability of unbalanced reporting was significantly increased in stories about a new treatment, procedure, test or product (22/49, 45%), compared to stories covering common treatments or basic scientific research (5/97, 5%) (risk ratio, 8.72). Conclusions/Significance Consistent with prior research on health science communication in other countries, we report undisclosed costs and risks, emphasized benefits, unrevealed financial conflicts of interest and exaggerated claims in Italian print media. In addition, we show that the risk for a story about a new medical approach to be unbalanced is almost 9 times higher with respect to stories about any other kind of health science-related topics. These findings raise again the fundamental issue whether popular media is detrimental rather than useful to public health.

Semiautomated labelling and fractionation of yttrium-90 and lutetium-177 somatostatin analogues using disposable syringes and vials

ObjectivesThe treatment of tumours expressing somatostatin receptors with yttrium-90 (90Y)-labelled and lutetium-177 (177Lu)-labelled somatostatin analogues is one of the most interesting therapeutic approaches adopted in nuclear medicine in recent years. However, the process of synthesis and fractionation of these radiopharmaceuticals is still mainly carried out manually despite the high radiation exposure to the operators and the need to comply with good manufacturing practices. In this study a semiautomatic synthesizer [automatic dose dispenser (ADD-2)] using only disposable syringes and vials has been presented. Materials and methodsSmall-scale syntheses (185–555 MBq) of 90Y/177Lu-DOTATATE were performed by adding the appropriate amount of peptide to a 90Y/177Lu chloride solution (n=10). The radionuclide/peptide molar ratio was 1 : 17 and 1 : 2 for 90Y and 177Lu, respectively. The solutions were buffered to 4.6 pH by ascorbate buffer and heated at 90°C for 30 min. Radiochemical purity was assessed by two independent radio-thin-layer chromatography systems. The solutions were fractioned to mimic the preparation of patient doses. ResultsAll synthesis and fractionation steps were performed using ADD-2. The radiochemical yield was 92±3% for 90Y and 97±1% for 177Lu labelling. Radiochemical purity was more than 99.5%. The accuracy and reproducibility of the instrument in transferring and fractionating radioactive solutions were high (maximal error ∼5%). ConclusionADD-2 appears suitable for use in clinical preparations of 90Y/177Lu-DOTATATE with therapeutic amounts of precursors (20–30 GBq). The operator’s exposure to radiation by using ADD-2 in comparison with manual preparations is under investigation.

Comparison of Different Positron Emission Tomography Tracers in Patients with Recurrent Medullary Thyroid Carcinoma: Our Experience and a Review of the Literature

Several morphological and functional imaging techniques are usually used to detect residual/recurrent medullary thyroid carcinoma (MTC) with variable results; currently, there is growing interest in positron emission tomography (PET) methodology. Herein, we report our experience of and a literature review about the comparison of different positron emission tomography (PET) tracers in patients with residual/recurrent MTC. (18)F-DOPA PET/CT seems to be the most useful imaging method to detect recurrent MTC lesions, performing better than (18)F-FDG and (68)Ga-somatostatin analogs PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with aggressive tumors. (68)Ga-somatostatin analogs PET/CT may be useful to select patients who could benefit from radioreceptor therapy. The information provided by the various PET tracers reflects different metabolic pathways, and may help to select the most appropriate treatment.

Functional Imaging Evaluation in the Detection, Diagnosis, and Histologic Differentiation of Pulmonary Neuroendocrine Tumors

Pulmonary neuroendocrine tumors (pNETs) have distinct pathologic characteristics. Typical carcinoids are indolent neoplasms with a good prognosis, whereas atypical carcinoids have a less indolent behavior. Both are optimally treated with complete surgical excision. More aggressive pNETs often present with local invasion, thoracic lymph nodal metastases, and distant spread. Patients may not be candidates for surgical resection and are treated with chemotherapy and/or radiation therapy. This article examines the potential role of functional imaging evaluation using (18)F FDG and somatostatin analogues labeled with (68)Ga DOTA-peptides in well-differentiated pNETs with particular attention to clinical and surgical implications.

Radiation protection procedures in 131I treatments for thyroid cancer in patients requiring hemodialysis

BackgroundHemodialysis is essential for patients with renal failure, and iodine-131 (131I) administration is the standard of care in thyroid carcinoma treatment. Although the need for hemodialysis during 131I treatment is very rare, it raises some concerns due to the involvement of personnel not exposed to radiation and to the contamination of devices used for other patients. In this paper, a radioprotection protocol to perform hemodialysis safely on patients during 131I treatment has been presented. Patients and methodsThe exposure of personnel who assisted 13 patients over the course of 10 years was monitored: external exposure was measured through electronic dosimeters, and internal contamination was checked by thyroid uptake and urine sample gamma spectrometry.Over this period, room layout was optimized to allow an improvement of radioprotection procedures.Two nurses were involved in patient assistance. ResultsAfter hemodialysis, measurements of internal contamination were below the minimum detectable activity and external exposure was in the range of 1–82 &mgr;Sv in terms of Hp(10).A reduction in personnel exposure was observed after hospitalization room renovation: Hp(10) normalized to the activity administered to the patient was about halved. ConclusionThe data show that hemodialysis can be performed safely during 131I treatments when appropriate radioprotection actions are implemented.