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Purpose: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99mTc-tilmanocept for SN biopsy. Methods: A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99mTc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer. Results: Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99mTc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88–1.01) and 0.99 (0.98–1.00) for breast cancer, 0.98 (0.96–0.99) and 1.00 (0.99–1.00) for melanoma, and 0.97 (0.93–1.02) and 0.99 (0.96–1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92–1.03). Conclusion: 99mTc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99mTc-tilmanocept is superior to other radiotracers used in clinical routine. [ABSTRACT FROM AUTHOR]

Purpose: Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. Methods: We conducted a retrospective study of 54 patients with FL (grade 1–3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34–85), stage was advanced (III–IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. Results: The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51–88) and 64 for WB-TLG (AUC 0.71; 95% CI 52–89) (p < 0.005). The probability of not having started treatment within 24 months was 87% for TMTV < 14 and 53% for TMTV ≥ 14 (p < 0.005). TMTV was independent of the FLIPI score for TTT prediction. Patients with both FLIPI ≥ 2 and TMTV ≥ 14 had only an 18% probability of not having started treatment at 36 months, while this probability was 75% in patients with TMTV < 14. Conclusion: Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies. [ABSTRACT FROM AUTHOR]

Purpose : To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods: Among 551 patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, 18F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman's rank correlation test. Results: Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p = 0.002). Conclusion: This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available. [ABSTRACT FROM AUTHOR]

Purpose : To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. Results: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). Conclusion: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion: In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to evaluate whether 18F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery. Methods: Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard. Results: At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVmax and SUVmean were significantly higher in pR0 than in pR1–pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1–pR2 than in pR0 patients. At final evaluation, SUVmax, SUVmean and TLG were significantly higher in pR1–pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUVmean, early delta TLG, and final delta SUVmax better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18F-FDG-PET/CT (93.5% and 92.3%, respectively). Conclusion: In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of 18F-FDG-PET/CT in early personalized treatment. The high NPV of early and final PET/CT could enable "tailored surgery" by avoiding lymphadenectomy in selected patients. [ABSTRACT FROM AUTHOR]

Objective: We assessed the prognostic value of several FDG PET/CT parameters, measured within the primary tumor and the involved lymph nodes, before definitive radio-chemotherapy (RCT) in anal cancer patients.Methods: Anal cancer patients with positive baseline FDG PET/CT who underwent definitive RCT from May 2011 to February 2018 were retrospectively assessed. Primary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, T-MTV, T-TLG, whole-body (WB) MTV, and WB-TLG were measured. Kaplan-Meier curves, Cox-regression analysis, and logistic regression machine-learning technique were used to test for associations between clinical data, metabolic parameters, and outcomes as overall survival (OS), disease-specific survival (DSS), metastatic-free survival (MFS), disease-free survival (DFS), local relapse-free survival (LRFS), and colostomy-free survival (CFS).Results: Fifty-nine patients were included in the study. Median follow-up was 28 months. Higher pre-treatment WB-MTV, T-TLG, and WB-TLG were associated with worse OS (p = 0.025, 0.021, and 0.02, respectively). PET parameters resulted also statistically significant for DSS, DFS, and CFS (p = 0.032, 0.043, 9 × 10-4 for WB-TLG). Cox analysis showed that PET parameters are significant predictors of OS, DSS, DFS, CFS, and LRFS. On multivariate analysis, age, stage, T-SUVpeak, WB-MTV, and T-TLG resulted significantly related to OS. A further stratification for patients with advanced stage (cT3-4 any N or any cT, N + ) showed that MTV and TLG, measured within the primary tumor and the involved nodes, are significantly higher in patients with a worse prognosis. In this subgroup, cut-off values of T- and WB-TLG as well as T- and WB-MTV showed a statistically significant correlation with clinical outcomes.Conclusions: Pre-treatment metabolic parameters measured within the primary tumor and the involved nodes may represent additional new biomarkers for estimating prognosis in anal cancer patients, especially in advanced stage patients. [ABSTRACT FROM AUTHOR]

Aim: To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI).Methods: Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard.Results: The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse.Conclusions: rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS).Methods: Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard.Results: The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p < 0.001). Patients with negative 5p-DS and patients with rPET <1.14 had a similar two-year PFS (86 and 87 %, respectively). Patients with a positive 5p-DS had a 2-year PFS of 27 %, while patients with rPET >1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively.Conclusions: rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "European Journal of Nuclear Medicine and Molecular Imaging" which appeared in the 14 June 2022 issue.

Purpose: To evaluate whether standardized uptake value (SUV) and/or metabolic rate of glucose (MRglu) are different among epithelioid, mixed, and spindle cell uveal melanomas, as well as between low and high risk melanomas; to correlate ultrasonographic data and metabolic parameters with histopathological features; and to assess the role of F-FDG PET/CT for evaluating prognosis. Methods: Of 34 eligible patients prospectively enrolled with clinical suspicion of medium/large uveal melanoma, 26 (15 men, mean age 62.8 ± 11.8 years) were evaluated. All patients underwent metastatic work-up, 3-D dynamic brain and whole-body F-FDG PET/CT, and surgery. Results: Of the 26 ocular lesions, 23 showed F-FDG uptake, with a sensitivity of 88 %. MRglu was significantly higher in the epithelioid cell melanomas than in the spindle cell melanomas, as well as in high-risk lesions than in low-risk lesions ( p = 0.01, p = 0.02, respectively). SUV and MRglu were correlated with histopathological features while ultrasonographic data were not. Conclusion: MRglu is useful for distinguishing the different cell types in uveal melanoma, as well as high-risk from low-risk lesions, while SUV is not. MRglu provides a more accurate evaluation of glucose consumption, whereas SUV provides only an estimation. In addition, the metabolic parameters correlate with histopathological features, well also reflecting cellular behaviour in ocular malignancy. A longer follow-up is needed to assess the role of F-FDG in evaluating prognosis. [ABSTRACT FROM AUTHOR]

Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns (F-DOPA and C-5-HTP) or specific receptor expression (Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, C-5-HTP performs better than F-DOPA even though its use is hampered by its complex production and limited availability and experience; Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy. [ABSTRACT FROM AUTHOR]

The assessment of hepatobiliary and pancreatic tumors is commonly achieved by ultrasound, computed tomography (CT), and magnetic resonance. The 2-[fluorine-18]fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET) detects increased glucose metabolism associated with neoplastic lesions, provides high accuracy in most cancer imaging applications and is now widely used in clinical practice. However, PET is not always useful and accurate knowledge of appropriate indications is essential for a proper clinical management. F-FDG is transported into cells and phosphorylated by the enzyme hexokinase to F-FDG-6-phosphate, which cannot proceed down the glycolytic pathway and therefore is accumulated in the malignant tissue. PET allows accurate quantification of FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values provide highly reproducible parameters of tumor glucose use (Weber et al., J Nucl Med 40:1771-1777, ). The recent development and diffusion of hybrid PET-CT scanners allows functional and anatomic data to be obtained in a single examination, improving lesion localization and resulting in significant diagnostic improvement (Wahl, J Nucl Med 45:82S-95S, ). Moreover, CT can be performed diagnostically with the use of intravenous and oral contrast and simultaneous PET-contrast-enhanced CT scanning appears to be an efficient method in cancer evaluation. However, in most centers, a low-dose CT is routinely performed without contrast media infusion. Proper patient preparation, scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. The role of PET and PET-CT in malignancies of the liver, biliary tract, and pancreas is here reviewed; normal patterns, representative cases, and common pitfalls are also presented. [ABSTRACT FROM AUTHOR]

The assessment of hepatobiliary and pancreatic tumors is commonly achieved by ultrasound, computed tomography (CT), and magnetic resonance. The 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) detects increased glucose metabolism associated with neoplastic lesions, provides high accuracy in most cancer imaging applications and is now widely used in clinical practice. However, PET is not always useful and accurate knowledge of appropriate indications is essential for a proper clinical management. (18)F-FDG is transported into cells and phosphorylated by the enzyme hexokinase to (18)F-FDG-6-phosphate, which cannot proceed down the glycolytic pathway and therefore is accumulated in the malignant tissue. PET allows accurate quantification of FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values provide highly reproducible parameters of tumor glucose use (Weber et al., J Nucl Med 40:1771-1777, 1999). The recent development and diffusion of hybrid PET-CT scanners allows functional and anatomic data to be obtained in a single examination, improving lesion localization and resulting in significant diagnostic improvement (Wahl, J Nucl Med 45:82S-95S, 2004). Moreover, CT can be performed diagnostically with the use of intravenous and oral contrast and simultaneous PET-contrast-enhanced CT scanning appears to be an efficient method in cancer evaluation. However, in most centers, a low-dose CT is routinely performed without contrast media infusion.Proper patient preparation, scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. The role of PET and PET-CT in malignancies of the liver, biliary tract, and pancreas is here reviewed; normal patterns, representative cases, and common pitfalls are also presented. [ABSTRACT FROM AUTHOR]

Several studies evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and positron emission tomography/computed tomography (PET/CT) in detecting recurrent medullary thyroid carcinoma (MTC) with conflicting results. Aim of our study is to meta-analyze published data about this topic. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through December 2011 and regarding FDG PET or PET/CT in patients with suspected recurrent MTC was carried out. Pooled detection rate (DR) on a per patient-based analysis was calculated to measure the diagnostic performance of FDG PET and PET/CT in this setting. A sub-analysis considering PET device used, serum calcitonin, carcino-embryonic antigen (CEA), calcitonin doubling time (CTDT), and CEA doubling time (CEADT) values was also performed. Twenty-four studies comprising 538 patients with suspected recurrent MTC were included. DR of FDG PET or PET/CT in suspected recurrent MTC on a per patient-based analysis was 59 % (95 % confidence interval: 54-63 %). Heterogeneity between the studies was revealed. DR increased in patients with serum calcitonin ≥1,000 ng/L (75 %), CEA ≥5 ng/ml (69 %), CTDT <12 months (76 %), and CEADT <24 months (91 %). In patients with suspected recurrent MTC FDG PET and PET/CT are associated with a non-optimal DR since about 40 % of suspected recurrent MTC remain usually unidentified. However, FDG PET and PET/CT could modify the patient management in a certain number of recurrent MTC because these methods are often performed after negative conventional imaging studies. DR of FDG PET and PET/CT increases in patients with higher calcitonin and CEA values and lower CTDT and CEADT values, suggesting that these imaging methods could be very helpful in patients with more aggressive disease. [ABSTRACT FROM AUTHOR]

Objective: The aim of our preliminary study was to evaluate the potential role of 18F-FDG PET-CT in monitoring response to reduced-intensity conditioning (RIC) transplant in a small series of chronic lymphocytic leukemia (CLL) patients and to compare the results with those obtained by standard criteria. Methods: We retrospectively analyzed 9 consecutive refractory/relapsed CLL patients, who underwent RIC transplant from March 2004 until May 2009. PET-CT was planned at 6-8 months after transplant to assess response and at a mean of 6 months during follow-up. The mean long-term follow-up period was 38 months (range 12-74 months, median 29 months). Results: The first PET-CT showed abnormal 18F-FDG uptake in five patients, while by standard criteria eight patients showed persistent disease. At the end of follow-up (mean 38 months), all four patients with previously negative scan were still PET negative and in complete remission by standard criteria. All five patients with previously positive scan were still PET positive: one patient died for disease progression and four are alive with disease. Conclusions: Our preliminary data, although in a small series of CLL patients, suggest that the metabolic findings revealed at first PET-CT after transplant seem to predict the patient outcome and to assess the metabolic disease status earlier than clinical evaluation by standard criteria. PET-CT performed during follow-up may be useful to early detect disease progression. [ABSTRACT FROM AUTHOR]

Objective: The aim of our preliminary study was to evaluate the potential role of F-FDG PET-CT in monitoring response to reduced-intensity conditioning (RIC) transplant in a small series of chronic lymphocytic leukemia (CLL) patients and to compare the results with those obtained by standard criteria. Methods: We retrospectively analyzed 9 consecutive refractory/relapsed CLL patients, who underwent RIC transplant from March 2004 until May 2009. PET-CT was planned at 6-8 months after transplant to assess response and at a mean of 6 months during follow-up. The mean long-term follow-up period was 38 months (range 12-74 months, median 29 months). Results: The first PET-CT showed abnormal F-FDG uptake in five patients, while by standard criteria eight patients showed persistent disease. At the end of follow-up (mean 38 months), all four patients with previously negative scan were still PET negative and in complete remission by standard criteria. All five patients with previously positive scan were still PET positive: one patient died for disease progression and four are alive with disease. Conclusions: Our preliminary data, although in a small series of CLL patients, suggest that the metabolic findings revealed at first PET-CT after transplant seem to predict the patient outcome and to assess the metabolic disease status earlier than clinical evaluation by standard criteria. PET-CT performed during follow-up may be useful to early detect disease progression. [ABSTRACT FROM AUTHOR]

Introduction: We performed a meta-analysis on published data on the diagnostic performance of fluorine-18 dihydroxyphenylalanine (F-DOPA) positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). Materials and methods: A comprehensive computer literature search of studies published up to 31 January 2012 regarding F-DOPA PET or PET/CT in patients with CHI was performed. Pooled sensitivity and specificity, area under the ROC curve and diagnostic odds ratio (DOR) of F-DOPA PET or PET/CT in diagnosing focal CHI were calculated. The localization accuracy of focal CHI was also estimated. Seven studies comprising 195 CHI patients were included. Results: The pooled sensitivity and specificity of F-DOPA PET or PET/CT in differentiating between focal and diffuse CHI were 89% (95% confidence interval [CI]:81-95%) and 98% (95% CI:89-100%), respectively. The DOR was 74.5 (95% CI:18-307). The area under the ROC curve was 0.95. The pooled accuracy of these functional imaging methods in localizing focal CHI was 80% (95% CI:71-88%). Discussion: In CHI patients, F-DOPA PET or PET/CT demonstrated high sensitivity and specificity in differentiating between focal and diffuse CHI. F-DOPA PET or PET/CT are accurate methods of localizing focal CHI. Nevertheless, possible sources of false-negative results for focal CHI should be kept in mind. [ABSTRACT FROM AUTHOR]

Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91-95%) and 91% (95% CI: 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs. [ABSTRACT FROM AUTHOR]

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 (C) or Fluorine-18 (F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding C-choline or F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose (F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG). Methods: A comprehensive computer literature search of studies published through 30 June 2011 regarding F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed. Results: Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of F-DOPA PET or PET/CT was found. A significant increase in sensitivity of F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed. Conclusion: In patients with suspected PG F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence F-DOPA PET or PET/CT diagnostic performance. [ABSTRACT FROM AUTHOR]

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

The utilization of 2-[fluorine 18] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in combination with computed tomography (CT) in the assessment of gynecologic malignancies has been rapidly growing in recent years; however, its role in clinical practice has yet to be established. A number of pitfalls are commonly encountered, including normal physiologic activity in bowel loops and blood vessels, or focal retained activity in ureters and urinary bladder. Increased uptake has also been reported in many benign pelvic processes and in premenopausal patients; endometrial activity changes cyclically, whereas increased ovarian uptake may be functional. FDG PET-CT has an emerging role in staging nodal disease and in the evaluation of local recurrence or peritoneal spread of gynecologic malignancies and is also useful in monitoring response to therapy and in long-term follow-up. FDG PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data. Patient preparation, proper scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Early diagnosis of peritoneal spread in malignant disease is essential to prevent unnecessary laparotomies and to select the patients in whom complete cytoreduction is feasible. Although anatomic imaging is the mainstay for evaluating peritoneal seeding, small neoplastic implants can be difficult to detect with CT and MR imaging. FDG PET-CT has the potential to improve detection of peritoneal metastases as lesion conspicuity is high at PET due to low background activity and fused PET-CT offers the combined benefits of anatomic and functional imaging. Correlation of uptake modalities with the pathogenesis of intraperitoneal spread of malignancies, provides a rational system of analysis and is essential to define disease. Distinct patterns appear to predict the presence of either nodular or diffuse peritoneal pathology. Main pitfalls are related to normal physiologic activity in bowel loops and blood vessels or focal retained activity in ureters and urinary bladder. PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data and in selecting patients for complete cytoreduction. FDG PET-CT adds to conventional imaging in the detection and staging of peritoneal carcinomatosis and is a useful diagnostic tool in monitoring response to therapy and in long term follow-up. [ABSTRACT FROM AUTHOR]

The most common causes of hyperaldosteronism (HA) are bilateral idiopathic hyperaldosteronism (IHA), aldosterone-producing adenoma (APA), and unilateral primary adrenal hyperplasia (PAH). We evaluated if non-invasive preoperative imaging studies are able to reliably differentiate these causes of hyperaldosteronism. The medical records of 50 consecutive patients with HA were reviewed. Follow up was obtained by outpatient consultation or phone contact. Thirty-five patients (70%) underwent successful adrenalectomy for APA, basing on the computed tomography (CT) scan results only. All these patients were biochemically cured. The remaining 15 patients underwent dexamethasone suppression adrenal cortical scintiscan (ACS) because of equivocal or inconclusive CT scan. In 11 of these patients, ACS showed a bilateral uptake, suggesting IHA. They were followed-up. In the remaining four patients, ACS showed a unilateral uptake. These patients underwent adrenalectomy. Final histology showed APA in three patients and PAH in one. They were biochemically cured. Sensitivity of combined non-invasive imaging procedures (CT and ACS) in detecting histologically proven and biochemically cured APA and PAH was 100%. Non-invasive adrenal imaging studies are accurate in distinguishing between IHA and APA/PAH. Invasive diagnostic tests (adrenal venous sampling) should be indicated only when they do not conclusively localize hypersecretion. [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the reliability of radioiodine (131I) and a gamma probe for radio-guided surgery (RGS) to detect and then radically dissect lymph node recurrences (LNRs) in 10 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of an iodine-positive LNR after previous total thyroidectomy and at least two ineffective 131I treatments. The protocol was designed as follows. Day 0: all patients were hospitalized and received 3.7 GBq of 131I in the hypothyroid condition. Day 3: presurgery whole-body scan with a therapeutic dose (TxWBS). Day 5: neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio. Day 7: post-surgery TxWBS performed using the remaining radioactivity. The presurgery TxWBS was positive in all patients, and the post-surgery TxWBS showed a negative pattern in 7 of 10 patients, suggesting the efficacy of the surgical procedure in most of the patients. After RGS the mean decrease in the absolute counts and the L/B counts ratio were 77.6% (52.7% minimum, 94.6% maximum) and 77.4% (52.3% minimum, 94.8% maximum), respectively. After operation the surgeon judged the procedure to be decisive in two patients, favorable in six, and irrelevant in two. The final histologic examination showed the presence of 78 lymph node metastases (mean of 8 per patient). There were 33 neoplastic lesions found by both TxWBS and gamma probe evaluations; 41 were shown only by gamma probe, and 4 were negative by both TxWBS and gamma probe evaluations. This protocol permitted us to look for neoplastic foci with high sensitivity and specificity, and we were able to remove lymph node metastases resistant to radioiodine therapy at a single session. The protocol also allowed detection of some additional tumoral foci in sclerotic areas or behind vascular structures that are difficult to identify and were not seen at the presurgery TxWBS evaluation. However, because of the possible false-negative results, complete excision must be undertaken in high risk patients with a local recurrence to eradicate the largest number of lymph nodes, independent of the counts measured by the gamma probe. [ABSTRACT FROM AUTHOR]

Cystic lesions of the thyroid are common findings. Although many thyroid cysts are of benign, some cases of hemorrhagic degenerative changes occur in neoplastic nodules, mostly follicular neoplasms and papillary carcinomas. The occurrence of hemorrhagic changes in medullary carcinomas has never been documented with aspirative cytological and histological pictures to the best of our knowledge. A case of medullary thyroid carcinoma with a large central hemorrhagic cyst is described, and the literature regarding the pathogenesis of this regression and the occurrence of cystic neoplasms in the thyroid is reviewed. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB), a childhood radiosensitive tumor, is very aggressive and malignant; in its disseminated form, despite very intensive chemotherapy, prognosis continues to be dismal. Owing to its capacity to concentrate in NB lesions, large doses of 131-I-MIBG, have given very encouraging therapeutic results in patients resistant to conventional therapy as well as at diagnosis.We recently reported the first attempt in combination therapy (CO-TH) using 131-I-MIBG and cisplatin. This new form of CO-TH appears very effective in obtaining a rapid and excellent response in relapsed patients.In this report, we describe the results of further experience with CO-TH in disseminated NB. We have attempted to verify to what extent interaction between the effects of the two agents may produce therapeutic benefit, and we have sought the optimization of CO-TH use.Three stage IV NB patients were treated with CO-TH. The following treatment schedule, was planned: day 1, cisplatin 50 mg/m2 i.v. over 6 h; day 2, 131-I-MIBG 100—130 mCi at high specific activity (- 1.1 Gbq/mg) i.v. over 6 h followed, a week later, by the same treatment combination.The therapeutic results were encouraging. However, hematological toxicity continued to represent a major limiting factor. In view of the overall effectiveness of CO-TH, at the price of lasting hematological toxicity, it may be indicated as a consolidationregimen some time before conditioning chemotherapy for autologous bone marrow transplantation. [ABSTRACT FROM AUTHOR]

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in 'at risk' cases, surgery could be the most useful treatment. [ABSTRACT FROM AUTHOR]

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients.Results: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site.Conclusions: Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of “personalized medicine.” [ABSTRACT FROM AUTHOR]

The article presents the case of 43-year-old and 46-year-old sisters diagnosed with multiple endocrine neoplasia type-2A (MEN2A). The sisters experienced increased levels of urinary metanephrines and calcitonin. The article discusses how fluorine-18-dihydroxyphenylalanine(18F-DOPA) positron emission tomography/computed tomography (PET/CT) can detect various synchronous neuroendocrine tumors (NETs).

Purpose: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Methods: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Results: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Conclusion: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach. [ABSTRACT FROM AUTHOR]