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Lung cancer (LC) is currently one of the main causes of cancer-related deaths worldwide. Low-dose computed tomography (LDCT) of the chest has been proven effective in secondary prevention (i.e., early detection) of LC by several trials. In this work, we investigated the potential impact of radiomics on indeterminate prevalent pulmonary nodule (PN) characterization and risk stratification in subjects undergoing LDCT-based LC screening. As a proof-of-concept for radiomic analyses, the first aim of our study was to assess whether indeterminate PNs could be automatically classified by an LDCT radiomic classifier as solid or sub-solid (first-level classification), and in particular for sub-solid lesions, as non-solid versus part-solid (second-level classification). The second aim of the study was to assess whether an LCDT radiomic classifier could automatically predict PN risk of malignancy, and thus optimize LDCT recall timing in screening programs. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. The experimental results showed that an LDCT radiomic machine learning classifier can achieve excellent performance for characterization of screen-detected PNs (mean AUC of 0.89 ± 0.02 and 0.80 ± 0.18 on the blinded test dataset for the first-level and second-level classifiers, respectively), providing quantitative information to support clinical management. Our study showed that a radiomic classifier could be used to optimize LDCT recall for indeterminate PNs. According to the performance of such a classifier on the blinded test dataset, within the first 6 months, 46% of the malignant PNs and 38% of the benign ones were identified, improving early detection of LC by doubling the current detection rate of malignant nodules from 23% to 46% at a low cost of false positives. In conclusion, we showed the high potential of LDCT-based radiomics for improving the characterization and optimizing screening recall intervals of indeterminate PNs.

Funding Acknowledgements Type of funding sources: None. Background Patients undergoing chemotherapy (CHT) for breast cancer (BC) need a monitoring of cardiac function due to the possible onset of cardiotoxicity. Cardiotoxicity may occur with heart failure but is often asymptomatic and is detectable only by assessing an increase in cardiac volumes (left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes) and/or by a reduction of the left ventricular ejection fraction (LV-EF). The primary purpose of this study was to evaluate the role of gated SPECT myocardial perfusion imaging in this setting. Dosimetric evaluation was also assessed. Methods Seventeen BC patients (mean age 55.93 ± 11.04 years)with invasive ductal carcinoma HER2 + treated with surgery and with an anthracycline-based adjuvant CHT, were enrolled. The trend of cardiac function was assessed by evaluation of LV-EF, LV-EDV and LV-ESV using gSPECT in baseline conditions and at 12, 15 and 52 weeks during treatment and then at 6, 12, 24 and 48 months during follow-up. Each patient was studied 15-20 min after injection of 555 MBq of 99mTc-Tetrofosmin with gSPECT (16 frames/cardiac cycle) using an Infinia Hawkeye IV gamma-camera. Dosimetry was assed according to ICRP reports. Results Two out of the 17 patients enrolled left the protocol: one because of a second tumor and the other due to the appearance of cardiotoxicity. 15 patients completed the study: mean LVEF at baseline was 70.67 ± 5.68. The greatest modification occurred after 15th week of treatment, when mean LV-EF showed a significant decrease to 65.67 ± 8.27, while mean LV-EDV and mean LV-ESV increased from 73.60 ± 16.72 up to 84.73 ± 21.11 and from 21.93 ± 7.17 up to 30.27 ± 14.16, respectively. All parameters progressively returned similar to baseline values at the final examination (after 48th month): mean LV-EF 70.20 ± 5.65, LV-EDV 73.40 ± 16.15 and ESV 22.07 ± 7.50. In one case cardiotoxicity occurred at 15th week: LV-EF decreased from 69 to 47%, LV-EDV increased from 92 up to 142 ml and LV-ESV from 28 up to 75 ml. According to our image protocols, effective dose for gSPECT was 3.83 mSv (ICRP 106). The use of gSPET instead of MUGA (6.47 mSv–ICRP 80) allowed a dose effective saving of 2.64 mSv/each control with a total saving of 21.12 mSv/patient. Conclusions Although the small sample size, gSPECT was demonstrated to be an applicable tool for monitoring cardiac function because it correctly identified BC patient with cardiotoxicity. gSPECT also allowed a significant radiation dose saving compared to MUGA: this is particularly relevant in cardiotoxicity studies that require repeated and close evaluations.

This study used wastewater-based epidemiology (WBE) to investigate the lifestyle of the inhabitants of Male, the capital of the Republic of Maldives. Raw wastewater 12-h composite samples were collected from nine pumping stations serving the city area - thus representative of the whole Male population. Samples were analysed by liquid chromatography coupled to mass spectrometry for estimating the profile of use of a large number of substances including illicit drugs, alcohol, caffeine, tobacco and pharmaceuticals. The illicit drugs most used were cannabis (THC) and heroin (700 and 18 g/day), with lower consumption of cocaine and amphetamines (0.1–1.2 g/day). It is important to note that the consumption of cannabis in Male was comparable to that measured in other countries, while the consumption of heroin was higher. Among cathinones, mephedrone was detected at the highest levels similar to other countries. Consumption of alcohol, which is not allowed in Maldives, was found (1.3 L/day/1000 inhabitants), but at a low level compared with other countries (6–44 L/day/1000 inhabitants), while the consumption of caffeine and tobacco was generally in line with reports from other countries. Unique information on pharmaceuticals use was also provided, since no official data were available. Human lifestyle was evaluated by applying for the first time the full set of WBE methodologies available in our laboratory. Results provided valuable epidemiological information, which may be useful for national and international agencies to understand population lifestyles better, including illicit drug issues, and for planning and evaluation of drug prevention programs in Male.

In recent years, high-intensity focused ultrasound (HIFU) has emerged as a new and promising non-invasive and non-ionizing ablative technique for the treatment of localized solid tumors. Extensive pre-clinical and clinical studies have evidenced that, in addition to direct destruction of the primary tumor, HIFU-thermoablation may elicit long-term systemic host anti-tumor immunity. In particular, an important consequence of HIFU treatment includes the release of tumor-associated antigens (TAAs), the secretion of immuno-suppressing factors by cancer cells and the induction of cytotoxic T lymphocyte (CTL) activity. Radiation therapy (RT) is the main treatment modality used for many types of tumors and about 50% of all cancer patients receive RT, often used in combination with surgery and chemotherapy. It is well known that RT can modulate anti-tumor immune responses, modifying micro-environment and stimulating inflammatory factors that can greatly affect cell invasion, bystander effects, radiation tissue complications (such as fibrosis), genomic instability and thus, intrinsic cellular radio-sensitivity. To date, various combined therapeutic strategies (such as immuno-therapy) have been performed in order to enhance RT success in treating locally advanced and recurrent tumors. Recent works suggested the combined use of HIFU and RT treatments to increase the tumor cell radio-sensitivity, in order to synergize the effects reaching the maximum results with minimal doses of ionizing radiation (IR). Here, we highlight the opposite immuno-modulation roles of RT and HIFU, providing scientific reasons to test, by experimental approaches, the use of HIFU immune-stimulatory capacity to improve tumor radio-sensitivity, to reduce the RT induced inflammatory response and to decrease the dose-correlated side effects in normal tissues.

The introduction of 18-FDG-PET/CT during preoperative evaluation of patients with epithelial ovarian cancer (EOC) has led to an increase of the detection of extra-abdominal metastases. However, the clinical impact of this upstage remains unclear.Patients with suspected advanced EOC underwent 18-FDG-PET/CT within two weeks prior to debulking surgery.Between 2006 and 2011 95 patients met the inclusion criteria. Based on the concordance or the discrepancy of clinical and PET/CT stage, patients were divided into 3 groups (A: clinical and PET III; B: clinical III and PET IV; C: clinical and PET IV). Twenty-five patients were upstaged from FIGO stage III to stage IV by PET/CT. The proportion of patients who achieved a residual tumor1cm in group B and C was similar, whereas it was significantly lower compared to group A. Similarly, complete response to adjuvant chemotherapy was achieved more frequently in patients in group A. PFS was similar in the three groups (17, 17 and 12 months in group A, B and C), as well as OS (51, 41 and 35 months).PET/CT is able to detect distant metastases in EOC patients. The presence of extra-abdominal disease probably indicates a more aggressive disease which also shows a lower response to standard chemotherapy. However, upstaged patients have a similar prognosis compared to stage III patients, probably because intra-abdominal disease is more likely to lead patients to death. This might also explain why residual tumor is the most important prognostic factor for advanced EOC patients.

Purpose: The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients. METHODS: Thirteen lung cancer patients (six men, mean age 70.0 years, 1 small cell lung cancer, 12 non-small cell lung cancer) who were candidates for radiation therapy were prospectively enrolled and submitted to RG-PET/CT. Ungated free-breathing CT images obtained during a PET/CT study were visually contoured by the radiation oncologist to define standard clinical target volumes (CTV1). Standard PTV (PTV1) resulted from CTV1 with the addition of 1-cm expansion of margins in all directions. RG-PET/CT images were contoured by the nuclear medicine physician and radiation oncologist according to a standardized institutional protocol for contouring gated images. Each CT and PET image of the patient's respiratory cycle phases was contoured to obtain the RG-CT-based CTV (CTV2) and the RG-PET/CT-based CTV (CTV3), respectively. RG-CT-based and RG-PET/CT-based PTV (PTV2 and PTV3, respectively) were then derived from gated CTVs with a margin expansion of 7-8 mm in head to feet direction and 5 mm in anterior to posterior and left to right direction. The portions of gated PTV2 and PTV3 geometrically not encompassed in PTV1 (PTV2 out PTV1 and PTV3 out PTV1) were also calculated. RESULTS: Mean ± SD CTV1, CTV2 and CTV3 were 30.5 ± 33.2, 43.1 ± 43.2 and 44.8 ± 45.2 ml, respectively. CTV1 was significantly smaller than CTV2 and CTV3 (p = 0.017 and 0.009 with Student's t test, respectively). No significant difference was found between CTV2 and CTV3. Mean ± SD of PTV1, PTV2 and PTV3 were 118.7 ± 94.1, 93.8 ± 80.2 and 97.0 ± 83.9 ml, respectively. PTV1 was significantly larger than PTV2 and PTV3 (p = 0.038 and 0.043 with Student's t test, respectively). No significant difference was found between PTV2 and PTV3. Mean ± SD values of PTV2 out PTV1 and PTV3 out PTV1 were 12.8 ± 25.4 and 14.3 ± 25.9 ml, respectively. The percentage values of PTV2 out PTV1 and PTV3 out PTV1 were not lower than 10 % of PTV1 in 6/13 cases (46.2 %) and than 20 % in 3/13 cases (23.1 %). CONCLUSION: Our preliminary data showed that RG-PET/CT in lung cancer can affect not only the volume of PTV but also its shape, as demonstrated by the assessment of gated PTVs outside standard PTV. The use of a gating technique is thus crucial for better delineating PTV by tailoring the target volume to the lesion motion in lung cancer patients.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (?HCG) and in 4 with ?HCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ?HCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ?HCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ?HCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ?HCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

INTRODUCTIONOccult endometrial cancer after supracervical hysterectomy is very uncommon. Even if optimal management of those rare cases is still unproven, to guide the need for further therapies, restaging should be recommended in this situation.PRESENTATION OF CASEWe report of a 60-year old woman with occult high risk endometrial cancer after supracervical hysterectomy with morcellation. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer.DISCUSSIONIn high risk endometrial cancer surgical restaging is important, considering that 10–35% of cases can present pelvic nodal metastasis. To reduce the treatment related morbidity maintaining the benefit of surgical staging, with a negative preoperative PET/CT, we performed a laparoscopic SN mapping with cervical stump removing.CONCLUSIONThis report highlight the fact that SN mapping with cervical injection is a feasible and safe technique also without the uterine corpus after supracervical hysterectomy with morcellation.

PURPOSE: This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. METHODS: Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[(18)F]fluorine-2-deoxy-D: -glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. RESULTS: Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [(18)F]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. CONCLUSIONS: This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury.

Background: The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. Objective: To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. Design, setting, and participants: Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. Intervention: Patients underwent salvage lymph node dissection (LND). Measurements: Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) < 0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. Results and limitations: Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA < 4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR < 24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. Conclusions: Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. "Background: The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. Objective: To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. Design, setting, and participants: Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. Intervention: Patients underwent salvage lymph node dissection (LND). Measurements: Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) < 0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. Results and limitations: Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA < 4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR < 24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. Conclusions: Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved."

Objective: Nodal status is one of the most important findings in patients with early-stage cervical cancer that requires post-surgical adjuvant therapies and influences prognosis of patients. The purpose of this study was to determine the diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) in the detection of nodal metastases. Methods: From 2004 to 2010 women with Ib1-IIa < 4 cm cervical cancer underwent 18F-FDG-PET/CT followed by radical hysterectomy and pelvic lymphadenectomy in our institution. 18F-FDG-PET/CT images were analyzed and histopathological findings served as the reference standard. Diagnostic performance of 18F-FDG-PET/CT in nodal disease detection was reported in terms of accuracy value. A sub analysis of women with tumor diameter < 2 cm (group 1) or 2-4 cm (group 2) was performed in order to verify the efficacy of 18F-FDG-PET/CT in each group. Results: One hundred fifty-nine women were enrolled. 65% had squamous histotype and 51% had grade 3 disease. Median number of nodes dissected was 29 (range 11-61). 28/159 women (18%) showed nodal metastases. Overall patient-based sensitivity, specificity, positive and negative predictive value of 18F-FDG-PET/CT for detection of nodal disease were 32.1%, 96.9%, 69.2%and 87.0% respectively. Among the 97 (61%) women included in group 1, 8 had nodal metastases (8.2%) and 2 was discovered through 18F-FDG-PET/CT (25%), while 20/62 women of the group 2 (32.3%) had nodal involvement, of which 7 (35%) was detected by 18F-FDG-PET/CT. Conclusions: This study showed that 18F-FDG-PET/CT had low sensitivity and had a minimal clinical impact in the pretreatment planning of stage Ib1-IIa < 4 cm cervical cancer. © 2011 Elsevier Inc. All rights reserved.

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation,metabolic activity can bemeasured by positrone-mission tomography imaging of [18F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolicactivitywasmeasuredfromthe[18F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H2O, and with regional VT normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment- derecruitment and increased metabolic activity. Copyright © 2011 American Thoracic Society.

PURPOSE: We assessed the value of [(11)C]choline positron emission tomography/computerized tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging. MATERIALS AND METHODS: Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [(11)C]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1) previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%). RESULTS: Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p

Objective The purpose of this study was to assess the value of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([F-18]FDG PET/CT) in the primary staging of high-risk endometrial cancer patients. Methods This retrospective study was conducted on 32 consecutive patients with histological diagnosis of primary high-risk endometrial cancer, who underwent PET/CT with [F-18]FDG in addition to conventional clinical and instrumental staging procedures. After surgery, [F-18]FDG PET/CT findings were correlated with pathological findings on a patient-by-patient basis. The diagnostic accuracy of [F-18]FDG PET/CT for primary cancer detection, lymph nodal involvement and distant metastases was assessed. Results [F-18]FDG PET/CT could correctly detect primary tumor in 29 of the 32 high-risk patients, with a sensitivity of 90.6%. The overall [F-18]FDG PET/CT patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 57.1, 100.0, 100.0, 86.4, and 88.5%, respectively, for revealing lymph nodal neoplastic involvement, and 100.0, 96.0, 87.5, 100.0, 96.9%, respectively, for detecting distant metastases. In particular, while the suspicion of distant metastases was documented by conventional imaging in only two patients, [F-18]FDG PET/CT correctly identified metastatic lesions in seven patients (21.9% of cases). Conclusion The major benefit provided in high-grade tumor patients by the use of [F-18]FDG PET/CT in the primary staging of endometrial cancer is its ability to accurately detect distant metastases in the abdomen and extra-abdominal regions. [F-18]FDG PET/CT adds relevant information that may influence patient management. Nucl Med Commun 31: 506-512 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background. High risk clinical stage I endometrial cancer (grade 2 and deep myometrial invasion, grade 3 and serous and clear-cell carcinoma) had 10-35% of nodal involvement. Surgical staging is considered reasonable in this setting of women, although unnecessary in 70-90%. The Purpose of this study was to determine prospectively the diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography 18F-FDG PET/CT in the detection of nodal metastases in patients with high Fisk endometrial cancer. Methods. Eleven women with grade 2 and deep myometrial invasion and 26 with grade 3 endometrial cancer underwent 18F-FDG PET/CT, followed by total hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy. Histopathological findings served as the reference standard. Diagnostic performance of 18F-FDG PET/CT in nodal disease detection was reported in terms of accuracy value both in a patient-based and a lesion site-based analysis. Results. Pelvic nodes metastases were found at histopathological analysis in 9 of the 37 patients (24.3%). Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT for detection of nodal disease were 77.8%, 100.0%, 100.0%, 93.1% and 94.4%, respectively. Nodal lesion site-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT were 66.7%, 99.4%, 90.9%, 97.2% and 96.8%, respectively. Conclusion. This study shows that 18F-FDG PET/CT is an accurate method for the presurgical evaluation of pelvic nodes metastases. The high negative predictive value may be useful in selecting patients who only may benefit from lymphadenectomy, minimizing operative and surgical complications. (C) 2009 Elsevier Inc. All rights reserved.

BACKGROUND: Fluorodeoxyglucose-positron emission tomography (FDG-PET) has proven its value in the diagnosis of undetermined pulmonary lesions, lung cancer staging, and assessment of prognosis. Purpose of this study is to clarify whether standardized uptake value (SUV) can predict clinical outcome of computed tomography (CT) screening detected lung cancer. METHODS: We tested the predictive value of FDG-PET using SUV on long-term survival of 34 lung cancer patients, detected from 1035 heavy smokers > or = 50 years monitored by annual low-dose CT for 5 years, with a median follow-up of 75 months from diagnosis. FINDINGS: PET scan was performed in 34 (89%) of 38 lung cancer patients diagnosed during the 5 years of screening and was positive in 32 (94%). Complete resection was achieved in 30 cases (88%), 20 (59%) were pathologic stage I and 23 (68%) were adenocarcinoma. Median SUV was 5.0 overall, being significantly lower in stage I (2.5 vs. 10.1, p = 0.001) and in adenocarcinoma (2.5 vs. 13.0, p = 0.001). The 5-year survival of lung cancer patients was 100% for SUV levels < or = 2.5, 60% for SUV more than 2.5 and less than 8, and only 20% for SUV > or = 8 (p = 0.001). CONCLUSIONS: FDG-PET using SUV can predict long-term survival of screening detected lung cancer, in a noninvasive manner. Metabolic assessment of biologic behavior might improve the clinical management of CT-detected lung cancer and reduce the risk of unnecessary treatments for indolent disease.

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

PURPOSE:: Positron emission tomography/computed tomography (PET/CT) with C-11 choline has been used for staging, restaging, and follow-up of various tumors, whereas its role for imaging meningiomas has only been preliminarily explored. The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F-18 FDG) uptake in meningiomas and relate these findings to the histopathological analysis. METHODS:: Two sequential three-dimensional PET/CT scans with 370 MBq (10 mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours apart in 7 patients with histologically confirmed meningiomas. Five patients had WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional regions of interest were drawn on tumor boundaries and on the contralateral side on CT images and copied to the corresponding PET images. SUVmax and tumor-to-background ratio were calculated. RESULTS:: Relative to the contralateral side, C-11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was decreased in 6 patients and increased in 1 of the 2 patients with grade II meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 +/- 1.3 and 5.7 +/- 1.3, respectively. The tumor-to-background ratio for C-11 choline was much higher than that for F-18 FDG (5.3 +/- 0.8 vs. 0.9 +/- 0.2, respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with grade II than in grade I meningiomas. CONCLUSIONS:: These preliminary results suggest that C-11 choline may better image meningiomas in comparison with F-18 FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of meningiomas need to be assessed in further studies.

Dear Sir, Anti-androgenic therapy compromises not only the quality of life of many unfortunate men with prostate cancer (PCa), but also makes the lives of diagnosticians uncomfortable. In a recent paper published in the EJNMMI, Giovacchini et al. [1] reported their experience using [C]choline PET/CT for detecting PCa in 12 hormone-naive patients and seven patients with anti-androgenic treatment for PCa. All patients had PCa, known from a pre-imaging biopsy and confirmed by later radical prostatectomy and routine sextant histopathological analysis, which was used as gold standard for imaging results. The authors present a detailed report of the results of histopathological sextant analysis and sextant SUVmax of [ C]choline above a threshold of 2.5, used as a surrogate marker for malignancy (Table 2 of ref. [1]). From these data, it is immediately clear that, in all hormone-naive patients, at least two sextants with histopathologically demonstrated PCa were correctly identified by SUVmax of [C]choline, resulting in a sensitivity of 100% for detecting PCa on a patient basis in this patient sample of 12 subjects. Seven patients under anti-androgenic treatment had virtually identical serum PSA concentrations (10.3±7.9 vs 12.9± 8.4 ng/ml, p=0.7) and lower SUVmax of [ C]choline (3.1± 1.0 vs 5.4±1.7, p 10 mm movement between PET and CT depending on bladder and bowl distension and a sampling error due to different slice thickness of histopathology (10 μm) and PET (4–5 mm), rendering comparative evaluation of histopathology and imaging very difficult. Nevertheless, complete demonstration of all intra-prostatic multi-focal manifestations of PCa by any non-invasive imaging modality is one of the hot unresolved issues in diagnostic oncologic imaging, whereas as shown in Table 2 of ref. [1], two of six sextants afflicted by PCa could be demonstrated with [C]choline PET/CT in hormone-naive patients similar to the results reported by other authors [3–5]. T-staging of PCa involves the assessment of capsular penetration, seminal vesical infiltration and/or infiltration of neurovascular bundles, structures which can only be reliably imaged with MRI, thus needing the latter imaging approach [6] for staging purposes. Finally, we find it difficult to draw any conclusions on clinical management based on 12 evaluable patients: this Eur J Nucl Med Mol Imaging (2008) 35:1740–1741 DOI 10.1007/s00259-008-0839-5

Purpose The aim of this study was to evaluate the role of PET/CT and sentinel lymph node (SLN) biopsy in staging high-risk endometrial cancer patients (G2 and deep myometrial invasion, G3, serous clear cell carcinoma or carcinosarcoma) in early clinical stage. Patients and Methods From January 2006 to December 2012, high-risk early-stage endometrial cancer patients performing PET/CT scan followed by surgery (systematic pelvic ± aortic lymphadenectomy) were included. From December 2010, SLN mapping with 99mTc-albumin nanocolloid and blue dye cervical injection was included in our clinical practice and additionally performed. Histological findings were used as the reference standard. Results Ninety-three patients were included, of which 22 of 93 had both PET/CT and SLN biopsy. The median number of dissected lymph nodes (LNs) was 28. Nineteen women (20.4%) had pelvic LN metastases; 14 were correctly identified by PET/CT. Among 5 false-negative cases, 3 occurred after the introduction of SLN mapping due to detection of micrometastases by ultrastaging. On overall patient-based analysis, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic LN metastases were 73.7%, 98.7%, 93.6%, 93.3%, 93.6%, respectively. Conclusions PET/CT demonstrated moderate sensitivity and high specificity in detecting pelvic LN metastases; its high positive predictive value (93.3%) is useful to refer patients to appropriate debulking surgery. Sentinel LN mapping and histological ultrastaging increased the identification of metastases (incidence, 18.3%-27.3%) not detectable by PET/CT because of its spatial resolution. The combination of both modalities is promising for nodal staging purpose.

PURPOSE: To prospectively evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of persistent ovarian carcinoma after first-line treatment, with use of histologic findings as the reference standard. MATERIALS AND METHODS: Thirty-one women (mean age, 55.9 years) with ovarian carcinoma treated with primary cytoreductive surgery and followed up with platinum regimen chemotherapy were included. All 31 patients were scheduled for surgical second-look. Before surgical second-look, all patients underwent fluorodeoxy-glucose (FDG) PET/CT. At PET/CT, three main categories of persistent disease were considered for data analysis: lymph nodal lesion, peritoneal lesion, and pelvic lesion. In all patients, imaging findings were compared with results of histologic examination after surgical second-look to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. The kappa statistic (Cohen kappa) was used for statistical analysis. RESULTS: Seventeen (55%) of 31 patients had persistent tumor at histologic analysis after surgical second-look, and fourteen (45%) had no histologically proved tumor. The total number of lesions that was positive for tumor cells at histologic analysis was 41 (lymph nodes, n = 16; peritoneal lesions, n = 21; pelvic lesions, n = 4); maximum diameter of these lesions was 0.3-3.2 cm (mean, 1.7 cm). A correlation was found between PET/CT and histologic analysis (kappa = 0.48). The overall lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 78%, 75%, 77%, 89% and 57%, respectively. In the detection of a tumor, a size threshold could be set at 0.5 cm, as this was the largest diameter of a lesion missed at PET/CT. CONCLUSION: Integrated PET/CT depicts persistent ovarian carcinoma with a high positive predictive value. (C) RSNA, 2004.

This work presents a method for CT and PET image registration, and multi-modal analysis, to optimize radiotherapy planning in lung cancer treatment. The method relies on an image registration technique based on fiducial external markers to realign, spatially, PET images with the CT spatial reference system. The method was set up for clinical use in radiotherapy, allowing minimal modifications to be introduced in the management of patients undergoing radiation treatment. The accuracy of the registration technique was evaluated on patient studies in terms of Target Registration Error and was found to be less than 6.40 mm. The method was applied in the treatment planning of five patients affected by non-small-cell lung cancer, revealing the usefulness of PET/CT integration in delineating the extension of both the tumor mass and the tissues involved in the neoplastic process. Moreover, the functional information provided by PET often led to alterations in the treatment planning, changing the size and/or direction of radiation portals. The proposed method for PET/CT integration has been confirmed as being useful for optimizing radiotherapy planning in lung cancer treatment.

The aim of this study was to retrospectively compare the value of integrated PET/CT and separate PET plus morphological imaging studies for lesion localisation in cancer patients. Two different series of consecutive patients who had previously been treated for neoplastic disease were considered. One series consisted of 105 patients who had undergone [(18)F]fluorodeoxyglucose (FDG) PET/CT ( n=70) or [(11)C]choline PET/CT ( n=35) studies (PET/CT group). The other series comprised 105 patients who had undergone FDG PET scan ( n=70) or [(11)C]choline PET scan ( n=35) alone; in this series, PET findings were correlated with the results of morphological imaging (MI) studies, i.e. CT ( n=92) or MR imaging ( n=13) (PET+MI group). Regions of abnormal tracer uptake at PET scanning were classified as ambiguous or unambiguous depending on their precise anatomical localisation. A total of 207 and 196 lesions were found in the PET/CT and PET+MI groups, respectively. The difference in terms of number of lesions per patient detected with the two imaging protocols was not statistically significant ( P=0.718). When analysis of lesion localisation was performed, there were 7/207 (3.4%) and 30/196 (15.3%) ambiguous lesions in the PET/CT and PET+MI groups, respectively. The number of ambiguous lesions was significantly higher in the PET+MI group than in the PET/CT group (chi(2)=15.768, P

Parkinson's disease is associated with slowness, especially of sequential movements, and is characterized pathologically by degeneration of dopaminergic neurons, particularly targeting nigrostriatal projections. In turn, nigrostriatal dopamine has been suggested to be critical for the execution of sequential movements. The objective of this study was to investigate in vivo, with [(11)C]raclopride, PET changes in regional brain levels of dopamine in healthy volunteers and Parkinson's disease patients during the execution of paced, stereotyped sequential finger movements. Striatal [(11)C]raclopride binding reflects dopamine D(2) receptor availability and is influenced by synaptic levels of endogenous dopamine. During execution of a pre-learned sequence of finger movements, a significant reduction in binding potential (BP) of [(11)C]raclopride was seen in both caudate and putamen in healthy volunteers compared with a resting baseline, consistent with release of endogenous dopamine. Parkinson's disease patients also showed attenuated [(11)C]raclopride BP reductions during the same motor paradigm in striatal areas less affected by the disease process. These findings confirm that striatal dopamine release is a component of movement sequencing and show that dopamine release can be detected in early Parkinson's disease during a behavioural manipulation.

Positron emission tomography/computed tomography (PET/CT) with C-choline is an established diagnostic tool for restaging prostate cancer patients with biochemical failure after primary treatment. In the present case, C-choline PET/CT was performed in a prostate cancer patient with skeletal metastases, treated with hormonal therapy. In addition to the detection of pathologic uptake at prostate and vertebra, C-choline uptake occurred in the neck. The finding was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally confirmed by parathyroid scintigraphy and histopathological analysis performed after hemithyroidectomy.

Using positron emission tomography (PET) and [(11)C]raclopride, an association between striatal D(2) dopamine receptors and emotional detachment has been recently reported. Several laboratory findings indicate a link between the serotoninergic system and harm avoidance. In this study we investigated, in a group of healthy volunteers, the relationship between the in vivo binding of 3-(2'-[(18)F]fluoroethyl) spiperone ([(18)F]FESP) to cortical 5HT(2) and striatal D(2) receptors and three personality dimensions, i.e., "novelty seeking," "reward dependence," and "harm avoidance." Eleven healthy volunteers were evaluated by means of the Tridimensional personality Questionnaire (C. R., Arch. Gen. Psychiatry 44: 573-588.) and underwent a PET scan with [(18)F] FESP. Harm avoidance showed a significant inverse correlation with [(18)F] FESP binding in the cerebral cortex, particularly in the frontal cortex (R (2) = -0.709, P = 0.0145) and left parietal cortex (R = -0.629, P = 0.038) but not in the basal ganglia (r = -0.176, P = 0.651). Similar results were obtained using SPM at a P threshold of 0.05. No significant correlation was observed with novelty seeking or reward dependence. In the cerebral cortex, high values of [(18)F]FESP binding values are associated with a high tendency to avoid danger, indicating involvement of the serotoninergic system and, in particular, 5HT(2A) receptors, in this trait of personality. The results of this as well as of previous studies on personality dimensions indicate the existence of a relationship between behavioral and neurobiological factors. In addition these results support the concept that the variability of PET data may be explained by neurochemical differences related to the prevalence of specific personality traits.

Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.

Purpose: To evaluate, in prostate cancer (PCa) patients the potential of 11C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. Methods: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on 11C-choline PET/CT only at the LN site. 11C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA 1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. Results: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. Conclusion: 11C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated 11C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate. © 2014 Springer-Verlag.

Objective: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations.Methods: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)).Results: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory.Conclusions: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Purpose: The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume - positron emission tomography (PET) gross tumour volume (PET-GTV). Methods: This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23-81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III-IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUVmax, SUVmean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUVmean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4-24 months). Results: MTV, TLG and PVC-TLG predicting patients' outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUVmean and PVC-SUVmean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results. Conclusion: FDG PET/CT uptake parameters are predictors of patients' outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters.

Objectives To evaluate the role of FDG PET/CT in the preoperative N-staging of high-risk clinical stage I endometrial cancer. The correlation between the metabolic characteristics of endometrial tumor uptake as predictors of a) lymph-node (LN) metastases and b) recurrence, was also evaluated. Methods Seventy-six high-risk (G2 with deep myometrial invasion, G3, serous/clear-cell carcinoma) clinical stage I endometrial cancer patients underwent preoperative PET/CT scan followed by total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy. PET/CT images were analyzed and correlated to histological findings. Maximal and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG, defined as the product between SUVmean and MTV) of endometrial lesions were calculated and correlated to: a) presence of LN metastases, b) recurrences. Results PET/CT resulted positive at LNs in 12/76 patients: 11/12 truly positive, 1/12 falsely positive. Conversely PET/CT was negative in 64/76 patients: 61/64 truly negative and 3/64 falsely negative. On pt-based analysis, sensitivity, specificity, accuracy, positive and negative predictive value of PET/CT in detecting LN metastases were 78.6%, 98.4%, 94.7%, 91.7%, 95.3%, respectively. A significant association was found between the presence of LN metastases and SUVmax (p=0.038), MTV (p=0.007), TLG (p=0.003) of the primary tumor. No correlations were found between the metabolic parameters and relapse (median follow-up 25.4months). Conclusions In high-risk clinical stage I endometrial cancer FDG PET/CT demonstrated moderate sensitivity, high specificity and accuracy for the nodal status assessment. SUVmax, MTV and TLG of the primary tumor are significantly correlated to LN metastases, while none of these parameters is predictor of recurrence.

Objective Positron emission tomography (PET)/computed tomography (CT) has been shown to be a valid tool in detecting lymph node (LN) metastases in men with biochemical recurrence after radical prostatectomy. We assessed its validity in detecting a single positive LN at pathologic examination in regard to an increasing interest in lesion-targeted salvage therapies. Methods and materials We included 46 patients with biochemical recurrence after radical prostatectomy and a single positive spot at [ 11 C]choline PET/CT who underwent pelvic or pelvic and retroperitoneal LN dissection. The ability of [ 11 C]choline PET/CT in identifying the exact positive LN was assessed with the positive predictive value (PPV) in the overall population and according to androgen deprivation therapy, prostate-specific antigen value, and site of PET/CT positivity. Results Overall, 30 patients (65%) had positive LNs at pathologic examination. Of these, only 16 (35%) had pathologically confirmed metastases in the same lymphatic region and 11 (24%) had involvement of 1 single LN. Conversely, 28 patients had positive LNs in other areas and 8 had no evidence of metastases. The overall PPV of PET/CT was 34.8% and 23.9% when exact concordance was defined according to the lymphatic landing site and single positive LN, respectively. The PPV ranged from 33.3% to 44.4% and from 17.9% to 28.6%, in men with and without androgen deprivation therapy, respectively. Conclusions The PPV [ 11 C]choline of PET/CT in correctly identifying patients with a single positive LN at salvage LN dissection is poor (24%). Therefore, extensive salvage treatment approaches are needed to maximize the chance of cure.

The potential impact of high-intensity focused ultrasound (HIFU) to general medicine and oncology seems very high. However, while in the research area, the development of this technique is very rapid and unchallenged. The direct application of HIFU to human tumour therapy is hampered by various technical difficulties, which may confine its role to a marginal device in the surgery armamentarium. To deploy the full potential of focused ultrasound in oncology, it seems necessary to review the basic relationship between HIFU and external beam radiotherapy. This is the aim of the present work.

Background: Diagnostic imaging plays a relevant role in the care of patients with breast cancer (BC). Positron Emission Tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has been widely proven to be a clinical tool suitable for BC detection and staging in which the glucose analog supplies metabolic information about the tumor. A limited number of studies, sometimes controversial, describe possible associations between FDG uptake and single nucleotide polymorphisms (SNPs). For this reason this field has to be explored and clarified. We investigated the association of SNPs in GLUT1, HIF-1a, EPAS1, APEX1, VEGFA and MTHFR genes with the FDG uptake in BC. Methods: In 26 caucasian individuals with primary BC, whole-body PET-CT scans were obtained and quantitative analysis was performed by calculating the maximum Standardized Uptake Value normalized to body-weight (SUVmax) and the mean SUV normalized to body-weight corrected for partial volume effect (SUVpvc). Human Gene Mutation Database and dbSNP Short Genetic Variations database were used to analyze gene regions containing the selected SNPs. Patient genotypes were obtained using Sanger DNA sequencing analysis performed by Capillary Electrophoresis. Results: BC patients were genotyped for the following nine SNPs: GLUT1: rs841853 and rs710218; HIF-1a: rs11549465 and rs11549467; EPAS1: rs137853037 and rs137853036; APEX1: rs1130409; VEGFA: rs3025039 and MTHFR: rs1801133. In this work correlations between the nine potentially useful polymorphisms selected and previously suggested with tracer uptake (using both SUVmax and SUVpvc) were not found. Conclusions: The possible functional influence of specific SNPs on FDG uptake needs further studies in human cancer. In summary, this is the first pilot study, to our knowledge, which investigates the association between a large panel of SNPs and FDG uptake specifically in BC patients. This work represents a multidisciplinary and translational medicine approach to study BC where, the possible correlation between SNPs and tracer uptake, may be considered to improve personalized cancer treatment and care.

Several case reports describing the coexistence of sarcoidosis and malignancy have been published. Therefore, sarcoidosis should always be considered as a differential diagnosis when a cancer patient develops lymphadenopathy. Positron-emission tomography (PET) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) combined with computed tomography (CT) is widely used for cancer staging and surveillance because it permits localization of metabolically active malignant tissue. PET/CT or CT findings in patients with suspected cancer recurrence can be used to guide early and aggressive therapy. However, benign hypermetabolic lymphadenopathy can mimic malignant lymphadenopathy, both on a conventional CT scan and on PET/CT. Thus, it is important to obtain a histological diagnosis before initiating antineoplastic therapy based on imaging findings. Four cases of patients affected by gynaecological malignancies and coexisting sarcoidosis are reported in this study. Furthermore, the clinical relevance of making a differential diagnosis between gynaecological cancer recurrence and granulomatous disorder is given specific mention.

PURPOSE: The effectiveness of salvage therapy in prostate cancer is greater for low prostate specific antigen values. Therefore, early detection of tumor recurrence is warranted. [(11)C]choline positron emission tomography/computerized tomography has the potential of early restaging of prostate cancer with low prostate specific antigen, but the selection of patients at high risk for positive [(11)C]choline positron emission tomography/computerized tomography is desirable to optimize salvage therapy. MATERIALS AND METHODS: This retrospective study included 75 patients with prostate cancer with an increasing prostate specific antigen less than 1.5 ng/ml after radical prostatectomy who never received antiandrogen deprivation therapy or salvage radiotherapy who underwent [(11)C]choline positron emission tomography/computerized tomography for the restaging of disease. Binary logistic regression was used to assess predictive factors of positive [(11)C]choline positron emission tomography/computerized tomography. Included variables were trigger prostate specific antigen, prostate specific antigen doubling time, age, pathological stage and Gleason score. RESULTS: Median prostate specific antigen was 0.61 ng/ml. [(11)C]choline positron emission tomography/computerized tomography was positive in 16 of 75 patients (21%). On univariate analysis prostate specific antigen doubling time less than 6 months was the only factor significantly associated with an increased risk of positive [(11)C]choline positron emission tomography/computerized tomography (OR 7.77, 95% CI 2.34-25.80, p = 0.001). In patients with prostate specific antigen doubling time less than 6 months, the positive detection rate of [(11)C]choline positron emission tomography/computerized tomography increased to 50%. CONCLUSIONS: In patients with prostate cancer with biochemical failure after radical prostatectomy and prostate specific antigen less than 1.5 ng/ml, prostate specific antigen doubling time less than 6 months predicts positive [(11)C]choline positron emission tomography/computerized tomography. In these patients [(11)C]choline positron emission tomography/computerized tomography may reduce by 50% the number in whom salvage therapy is initiated empirically without knowing the disease location.

Purpose: To assess the additional functional vascular information and the relationship between perfusion measurements and glucose metabolism (SUVmax) obtained by including a perfusion CT study in a whole-body contrast-enhanced PET/CT protocol in primary lung cancer lesions. Methods: Enrolled in this prospective study were 34 consecutive patients with a biopsy-proven diagnosis of lung cancer who were referred for contrast-enhanced PET/CT staging. This prospective study was approved by our institutional review board, and informed consent was obtained from all patients. Perfusion CT was performed with the following parameters: 80 kV, 200 mAs, 30 scans during intravenous injection of 50 ml contrast agent, flow rate 5 ml/s. Another bolus of contrast medium (3.5 ml/s, 80 ml, 60-s delay) was administered to ensure a full diagnostic contrast-enhanced CT scan for clinical staging. The perfusion CT data were used to calculate a range of tumour vascularity parameters (blood flow, blood volume and mean transit time), and tumour FDG uptake (SUVmax) was used as a metabolic indicator. Quantitative and functional parameters were compared and in relation to location, histology and tumour size. The nonparametric Kruskal-Wallis rank sum test was used for statistical analysis. Results: A cut-off value of 3 cm was used according to the TNM classification to discriminate between T1 and T2 tumours (i.e. T1b vs. T2a). There were significant perfusion differences (lower blood volumes and higher mean transit time) between tumours with diameter >30 mm and tumours with diameter 30 mm in diameter. Conclusion: Perfusion CT combined with PET/CT is feasible technique that may provide additional functional information about vascularity and tumour aggressiveness as a result of lower perfusion and higher metabolism shown by larger lesions.

Background The rate of nodal metastases in ovarian cancer macroscopically confined to the pelvis is about 15%–20%. Systematic pelvic and aortic lymphadenectomy improves staging but it is associated with increased morbidity and costs. The purpose of this study was to evaluate the role of 18F-FDG PET/CT in the pre-operative nodal metastases detection in ovarian cancer grossly confined to the pelvis. Methods From 2006 to 2012, 68 consecutive women with epithelial ovarian cancer confined to the pelvis underwent 18F-FDG PET/CT followed by surgery inclusive of systematic pelvic and aortic lymphadenectomy (SAPL). 18F-FDG PET/CT images were analyzed and correlated to histological examination. Results Twenty-six women underwent bilateral and 42 unilateral SAPL with 3165 nodes removed and analyzed. Median number of dissected nodes was 42 (range 16–91). Twelve women (17.6%) had nodal metastases. 18F-FDG PET/CT correctly identified 10 patients with nodal involvement. Sensitivity, specificity, accuracy, positive and negative-predictive value of 18F-FDG PET/CT in detecting nodal metastases were 83.3%, 98.2%, 95.6%, 90.9% and 96.5%, respectively, on overall patient-based, and 75.5%, 99.4%, 98.1%, 87.5% and 98.6%, respectively, on nodal lesion site-based analysis. Conclusion 18F-FDG PET/CT is an accurate tool for the detection of nodal metastases. Metabolic imaging could be used to select women who could benefit from systematic lymphadenectomy. The high negative predictive value allows avoidance of SAPL in the vast majority of women, minimizing operative and post surgical complications. Further larger prospective investigation is required to confirm our data.

A wide variety of learning and cognitive impairments have been identified in individuals with Turner's syndrome (TS), leading to diverse predictions regarding the neural substrates of TS. However, neuropathological studies have failed to identify any consistent structural abnormality in TS. Using positron emission tomography (PET), the current study provided a unique opportunity to examine patterns of cerebral glucose metabolism in girls with TS as compared to normal controls, and to examine diverse neuropsychological profiles of individual participants in relation to anatomical sites of metabolic dysfunction as identified with PET. TS girls with a wide range of cognitive functioning were chosen for study. PET studies in the awake, resting state were performed on 6 girls (ages 11–15 years) with TS (5 with some degree of cognitive or learning impairment; and for exploratory purposes, 1 with no history of learning or cognitive difficulties), and 6 age‐matched controls. Neuropsychological testing was also performed on the Turner girls. The 5 girls with TS having some degree of cognitive or learning impairment exhibited significantly lowered parietal metabolism as compared to the control group. However, when the nonimpaired TS girl was included in these analyses, the difference between groups did not reach significance. Four Turner girls exhibited glucose metabolism at or below the 30th percentile bilaterally in the parietal and lateral occipital cortical regions. The remaining 2 TS girls (1 with limited evidence of cognitive impairments and 1 who was free of cognitive impairments) exhibited normal or near‐normal glucose metabolism in these regions. Individual patterns of abnormal metabolic activity corresponded well with profiles of learning and cognitive impairments. These findings are generally consistent with those reported by Clark, Klonoff, and Hayden (1990) in suggesting that bilateral parietal and occipital lobe dysfunction may contribute to cognitive impairments in TS. Additionally, the present study underscores the heterogeneity of TS and suggests that our finding of parietal hypometabolism should not be generalized to TS individuals who are free of cognitive impairments

PURPOSE: The aim of our work is to evaluate the added diagnostic value of respiratory gated (4-D) positron emission tomography/computed tomography (PET/CT) in lung lesion detection/characterization in a large patient population of a multicentre retrospective study. METHODS: The data of 155 patients (89 men, 66 women, mean age 63.9 ± 11.1 years) from 5 European centres and submitted to standard (3-D) and 4-D PET/CT were retrospectively analysed. Overall, 206 lung lesions were considered for the analysis (mean ± SD lesions dimension 14.7 ± 11.8 mm). Maximum standardized uptake values (SUV(max)) and lesion detectability were assessed for both 3-D and 4-D PET/CT studies; 3-D and 4-D PET/CT findings were compared to clinical follow-up as standard reference. RESULTS: Mean ± SD 3-D and 4-D SUV(max) values were 5.2 ± 5.1 and 6.8 ± 6.1 (p < 0.0001), respectively, with an average percentage increase of 30.8 %. In 3-D PET/CT, 86 of 206 (41.7 %) lesions were considered positive, 70 of 206 (34 %) negative and 50 of 206 (24.3 %) equivocal, while in 4-D PET/CT 117 of 206 (56.8 %) lesions were defined as positive, 80 of 206 (38.8 %) negative and 9 of 206 (4.4 %) equivocal. In 34 of 50 (68 %) 3-D equivocal lesions follow-up data were available and the presence of malignancy was confirmed in 21 of 34 (61.8 %) lesions, while in 13 of 34 (38.2 %) was excluded. In 31 of these 34 controlled lesions, 20 of 34 (58.8 %) and 11 of 34 (32.4 %) were correctly classified by 4-D PET/CT as positive and negative, respectively; 3 of 34 (8.8 %) remained equivocal. With equivocal lesions classified as positive, the overall accuracy of 3-D and 4-D was 85.7 and 92.8 %, respectively, while the same figures were 80.5 and 94.2 % when equivocal lesions were classified as negative. CONCLUSION: The respiratory gated PET/CT technique is a valuable clinical tool in diagnosing lung lesions, improving quantification and confidence in reporting, reducing 3-D undetermined findings and increasing the overall accuracy in lung lesion detection and characterization.

OBJECTIVE: The purpose of this study was to assess whether there is an additional value of single-photon emission computed tomography/computed tomography (SPECT/CT) over lymphoscintigraphy (LSG) alone for sentinel node (SN) mapping in endometrial and cervical cancer. METHODS: Ten women with clinically cervical stage IA2 to stage IB1 and 25 women with stage I endometrial cancer underwent preoperative LSG for SN mapping. Technetium Tc 99m albumin nanocolloid was injected submucosally at 4 points of the cervix. Patients underwent SPECT/CT emission-transmission study at least 3 hours after standard planar images. Methylene blue was injected into the cervix just before surgery under general anesthesia. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and radical regional nodal dissection. Hot and/or blue nodes were labeled as SNs. RESULTS: Conventional planar imaging detection rate was 50%, whereas the detection rate of at least one SN with SPECT/CT was 91% (32/35); bilateral detection was achieved in 7 (39%) of 18 women in planar and in 17 (53%) of 32 women in SPECT/CT imaging, respectively. Bilateral detection was achieved in 57% of women (20/35). Sentinel nodes were located in external and internal iliac nodes (66%), obturator nodes (5%), internal iliac nodes (11%), common iliac nodes (9%), and presacral nodes (9%). Lymph node involvement was identified in 5 patients (14%). Sentinel node correctly predicted lymph node involvement in all node-positive patients. Sentinel node sensitivity and negative predictive value of SPECT/CT were 100%. CONCLUSIONS: Single photon emission computed tomography/computed tomography seems to improve intraoperative identification of SNs and provides additional useful information about the anatomic location of SNs compared to planar LSG in cervical and endometrial cancer.

The aim of this study was to evaluate the correlation between the changes of SUV(max) and of apparent diffusion coefficient (ADC) before and after neoadjuvant therapy, to enable us predict the therapy response, in patients with locally advanced rectal cancer (LARC). A total of 30 patients with LARC who underwent CRT were recruited for our study. All the patients underwent a whole body 18F-FDG-PET/CT scan and a pelvic MR examination including DW imaging for staging (PET/CT1 and RM1), and after the chemoradiation therapy (PET/CT2, and RM2). Histopathologic analysis of rectal specimen, according to tumor regression grade (Mandard's criteria) was used as the standard reference. MR and PET-CT images were analyzed, and measurements of ADC values and SUV(max) were taken. Diagnostic performance for selection of complete responders (TRG1-2) and overall diagnostic accuracy for each item were calculated. After neoadjuvant therapy, all patients were submitted to surgery. According to Mandard's criteria, 21 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; nine tumors were classified as non responders (TRG3, 4, and 5). In all the patients, mean value of SUV(max) in PET/CT1 was higher than those in PET/CT2 (P&nbsp

Purpose: We previously showed that prostate-specific antigen (PSA) doubling time (PSADT) is a significant predictor of C-11 choline positron emission tomography/computed tomography (PET/CT) findings in prostate cancer (PCa) patients. This study compared PSA velocity (PSAV) and PSADT to predict C-11 choline PET/CT findings. Materials and Methods: PSAV and PSADT were retrospectively calculated in 170 PCa patients with biochemical failure after radical prostatectomy, who underwent C-11 choline PET/CT for restaging of disease. Results: Median PSA was 1.25 ng/mL (range: 0.23-48.6 ng/mL), and median PSAV was 0.99 ng/mL/y (range: 0.11-98.9 ng/mL/y). Patients with positive C-11 choline PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with negative C-11 choline PET/CT (n = 95) (6.93 +/- 13.08 vs. 1.23 +/- 2.03 ng/mL/y). The percent of patients with positive C-11 choline PET/CT was 21% for PSAV 2 ng/mL/y. The quality of fitting (r(2)) of PSA values according to the exponential function (PSADT) was significantly (P < 0.05) better than the quality of fitting according to the linear function (PSAV) in the entire sample and in all anatomic regions. At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the statistical significance (P < 0.05). Conclusions: PSAV can be used to stratify the risk of positive C-11 choline PET/CT in PCa patients with biochemical failure. Patients with PSAV >1 ng/mL/y should be selected to increase the positive detection rate of C-11 choline PET/CT. The greater statistical power of PSADT compared with PSAV could be related to the better capability of fitting time-dependent changes in PSA values, thereby better reflecting the natural growth of recurrent PCa. Purpose: We previously showed that prostate-specific antigen (PSA) doubling time (PSADT) is a significant predictor of C-11 choline positron emission tomography/computed tomography (PET/CT) findings in prostate cancer (PCa) patients. This study compared PSA velocity (PSAV) and PSADT to predict C-11 choline PET/CT findings. Materials and Methods: PSAV and PSADT were retrospectively calculated in 170 PCa patients with biochemical failure after radical prostatectomy, who underwent C-11 choline PET/CT for restaging of disease. Results: Median PSA was 1.25 ng/mL (range: 0.23-48.6 ng/mL), and median PSAV was 0.99 ng/mL/y (range: 0.11-98.9 ng/mL/y). Patients with positive C-11 choline PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with negative C-11 choline PET/CT (n = 95) (6.93 +/- 13.08 vs. 1.23 +/- 2.03 ng/mL/y). The percent of patients with positive C-11 choline PET/CT was 21% for PSAV 2 ng/mL/y. The quality of fitting (r(2)) of PSA values according to the exponential function (PSADT) was significantly (P < 0.05) better than the quality of fitting according to the linear function (PSAV) in the entire sample and in all anatomic regions. At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the statistical significance (P < 0.05). Conclusions: PSAV can be used to stratify the risk of positive C-11 choline PET/CT in PCa patients with biochemical failure. Patients with PSAV >1 ng/mL/y should be selected to increase the positive detection rate of C-11 choline PET/CT. The greater statistical power of PSADT compared with PSAV could be related to the better capability of fitting time-dependent changes in PSA values, thereby better reflecting the natural growth of recurrent PCa.

18F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in 18F-FDG-PET/CT studies in oncology patients. © 2012 Elsevier España, S.L. and SEMNIM

PURPOSE: The aim of this study was to evaluate the clinical usefulness of [(11)C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa). METHODS: Seventy-eight consecutive patients with biochemical progression of PCa (mean prostate-specific antigen 21.1 ng/ml, range 0.2-500.0 ng/ml) referred for both [(11)C]choline PET/CT and BS for restaging purposes were retrospectively analysed. The diagnostic accuracy of [(11)C]choline PET/CT and BS was assessed by using morphological imaging and/or follow-up as standards of reference. As equivocal findings were found, the accuracy analysis was performed twice, once including them as positive and once as negative. A separate analysis was also performed in hormone-resistant patients and data compared with those of patients who did not receive anti-androgenic treatment. RESULTS: Equivocal findings occurred in 1 of 78 (1%) cases in [(11)C]choline PET/CT and in 21 of 78 (27%) cases in BS. Depending on their attribution as either positive or negative, the ranges of sensitivity, specificity, positive predictive value, negative predictive value and accuracy for [(11)C]choline PET/CT were 89-89%, 98-100%, 96-100%, 94-96% and 95-96%, respectively. For BS they were 100-70%, 75-100%, 68--100%, 100-86% and 83-90%, respectively. Concordant findings between [(11)C]choline PET/CT and BS occurred in 55 of 78 (71%) cases. The accuracy of [(11)C]choline PET/CT did not significantly (p = 0.30) differ between hormone-resistant patients (97%) and those who did not receive anti-androgenic treatment (95%). CONCLUSION: In clinical practice, [(11)C]choline PET/CT may not replace BS because of its lower sensitivity. However, for its high specificity, [(11)C]choline PET/CT positive findings may accurately predict the presence of BM. Equivocal findings are more frequent in BS than [(11)C]choline PET/CT.

Background Immortalized cancer cell lines are now well-established procedures in biomedicine for a more complete understanding of cellular processes in cancer. However, they are more useful in preparation of fresh tumour tissue, in order to obtain cancer cells with highly preserved individual tumour properties. In the present study we report an analytical investigation on a breast cancer primary cell culture isolated from a surgical specimen obtained from a patient with an infiltrating ductal carcinoma. The objective of the research was to reveal unrecognized aspects of neoplastic cells, typical of the tumour from where the cells were derived, but masked in fixed tissue sections, in order to better predict the aggressive potentiality of the tumour. Findings Using a combination of mechanical and enzymatic treatment, the tumour tissue was dissociated immediately after surgical removal. The primary cells were isolated by differential cell centrifugation and grown in selective media. Immunocytochemistry and quantitative RT-PCR analysis were performed to detect the presence of specific biomarkers at protein and transcript level. The isolated primary breast cancer cells displayed phenotypic behaviour, characteristic of malignant cells and expression of several mesenchymal markers, revealing a strong signature for the epithelial-to-mesenchymal transition associated to a stellate morphology with a number of cellular protrusions and the attitude to overgrow as multilayered overlapping cellular foci. Conclusions Our data are a further meaningful indication that primary cell cultures represent a powerful system that could be applied to those cases deserving a deeper investigation at molecular level in order to design individualized anticancer therapies in the future.

We have studied seven patients with Spielmeyer-Vogt disease (SV), aged 11-29 years, using PET and 2-deoxy-2[18F]fluoro-D-glucose. Five patients showed a distinctive age-related progression with decreased metabolic activity starting in the calcarine area and spreading rostrally to the entire cortex, leaving normal uptake only in the basal ganglia and brainstem of the oldest patients. Calcarine hypometabolism was mild in the youngest patient. All patients, including the youngest when the study was repeated 2 years later, had significantly decreased calcarine metabolic activity (P = 0.002). Two patients had PET patterns markedly different from the five others, with significantly decreased metabolic activity in most brain areas. Both patients may represent a new SV variant. An adult pathological control with congenital amaurosis showed normal cerebral metabolic activity in all areas. Two patients had older sisters, one now deceased, the other not available for study, who presented a rapid regression associated with epilepsy. Phenytoin and carbamazepine probably caused increased seizure activity and faster regression. The younger siblings treated with phenobarbital monotherapy had few seizures and maintained motor functions 5-8 years longer compared with their respective sisters. While the clinical course made obvious that some areas, such as the macula, are damaged before others, the progression from the calcarine area to the more anterior regions (but sparing the basal ganglia) provides unexpected insights into selective vulnerability of neurons that will allow a more precise way of monitoring individual patients.

PURPOSE OF REVIEW: To evaluate the role of PET/computed tomography (CT) imaging in patients with prostate cancer and to provide clinical recommendations, both in pretreatment and in post-treatment phase. RECENT FINDINGS: The potential role of PET/CT for evaluating intraprostatic disease, staging and restaging prostate cancer patients has been largely investigated. In particular, among the different PET tracers evaluated, choline, acetate and fluoride are showing the most promising results for imaging prostate cancer and its metastases. However, although choline PET/CT is an established diagnostic tool for imaging prostate cancer patients, as documented by a large amount of literature, further studies are still necessary to establish the final clinical role of PET/CT with acetate and fluoride. SUMMARY: Choline PET/CT is clinically indicated to noninvasively restage, in one single session, prostate cancer patients presenting a progressive increase of prostate-specific antigen, after radical treatment. Conversely, choline PET/CT does not allow the accurate assessment of intraprostatic tumor and of small lymph nodal involvement, thus not being currently recommended as a first-line method for initial diagnosis and staging. The current use of PET/CT with acetate and fluoride in clinical practice still needs further confirmations

The integrated modality positron emission tomography/computed tomography (PET/CT) with C-11 choline is an established diagnostic tool for restaging prostate cancer patients with a biochemical failure after primary treatment. Thymoma is a rare tumor originating in thymus epithelial cells, asymptomatic in one-third to one-half of patients, and often occurring in the fourth and fifth decades of life. In the present case, C-11 choline PET/CT was performed in a prostate cancer patient with a biochemical relapse, to restage the disease. In addition to the detection of local recurrent disease in prostatic fossa, an abnormal C-11 choline increased uptake in mediastinum was reported. The mediastinal finding was initially wrongly interpreted by clinicians as a lymph nodal metastasis from prostate cancer. However, histopathological analysis confirmed the presence of a thymoma. Although rare, thymoma has to be considered as differential diagnosis in case of mediastinal masses presenting C-11 choline PET/CT positive findings, to avoid inappropriate patient management.

Partial Volume Effect (PVE) in PET-CT oncological studies affects the estimation of quantitative parameters useful for lesion malignancy differentiation and for monitoring disease and response to therapy. The aim of this work was to investigate the clinical feasibility and accuracy of PVE correction methods based on Recovery Coefficients (RC) as function of measured Lesion-to-Background ratio (L/B)m and measured lesion volume (V)m. PET-CT measurements were performed. The radioactivity concentration (C)m and Vm were measured from images using Operator-Dependent and Operator-Independent (OI) techniques. RC curves were obtained combining RC from NEMA 2001 IQ phantom measurements as function of Sphere-to-Background ratio (S/B)m and sphere Vm. PVE correction was applied to PET-CT studies of anthropomorphic oncological phantoms and to PET-CT oncological studies (basal and follow up). The underestimation of Cm due to PVE in the NEMA IQ spheres (up to 80%) confirmed the severity of the error. The more feasible (always applicable, noise insensitive, reproducible) way to measure radioactivity was found by the use of an OI threshold technique. Our results showed that this measurement technique allows to achieve a PVE correction accuracy > 87% (error in radioactivity estimate < 13%) for a sphere diameter > 1 cm. In patient studies the PVE correction was found to modify both SUV and SUV variations during patient follow up and our analysis showed that a PVE corrected SUV quantification increases the diagnostic confidence of oncological PET-CT studies. Partial Volume Effect (PVE) in PET-CT oncological studies affects the estimation of quantitative parameters useful for lesion malignancy differentiation and for monitoring disease and response to therapy. The aim of this work was to investigate the clinical feasibility and accuracy of PVE correction methods based on Recovery Coefficients (RC) as function of measured Lesion-to-Background ratio (L/B)m and measured lesion volume (V m). PET-CT measurements were performed. The radioactivity concentration (Cm) and Vm were measured from images using Operator-Dependent and Operator-Independent (OI) techniques. RC curves were obtained combining RC from NEMA 2001 IQ phantom measurements as function of Sphere-to-Background ratio (S/B)m and sphere Vm. PVE correction was applied to PET-CT studies of anthropomorphic oncological phantoms and to PET-CT oncological studies (basal and follow up). The underestimation of Cm due to PVE in the NEMA IQ spheres (up to 80%) confirmed the severity of the error. The more feasible (always applicable, noise insensitive, reproducible) way to measure radioactivity was found by the use of an OI threshold technique. Our results showed that this measurement technique allows to achieve a PVE correction accuracy > 87% (error in radioactivity estimate < 13%) for a sphere diameter > 1 cm. In patient studies the PVE correction was found to modify both SUV and SUV variations during patient follow up and our analysis showed that a PVE corrected SUV quantification increases the diagnostic confidence of oncological PET-CT studies. © 2011 IEEE.