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Aim: To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUV max (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.

Background: The aim of this study was to verify the feasibility, in clinical practice, of three simplified methods (Hunter, Sadato and another one proposed by our group) to calculate Ki and MRglu of 18F-FDG, comparing the results with those derived by the linear regression (LR) method (considered the golden standard), and also with SUV., Methods: Forty-five patients (32males, mean age 69±9years) with non-small-cell-lung cancer prospectively enrolled, underwent dynamic 18F-FDG PET-CT over the thorax. Ki was estimated as follows: from a static acquisition and performing one venous blood sampling using the Hunter method; multiplying the SUV for the average plasma clearance rate (kP(T)) and for the initial distribution volume (V0bw) without performing any blood sampling using the Sadato method; multiplying the SUV for a factor F (which encompasses the mean value of haematocrit and plasma volume, both according to patient's sex) without performing any blood sample using ours method. Wilcoxon signed rank and coefficient of determination (R2) were used for statistical analysis., Results: No significant difference was observed between the Ki and MRglu estimated by all three simplified methods and the Ki and MRglu estimated by LR. The highest P values and the lower values of mean differences were observed with our method compared with LR: Ki=0.0392±0.0178 min-1 vs. Ki=0.0392±0.0202 min-1 (P=0.897, MD=0.0001 min-1), respectively; MRglu= 4.47±2.23 ml/min/100g vs. MRglu= 4.43±2.38 ml/min/100g (P=0.839, MD= -0.0373 mL/min/100g), respectively. The highest correlation was observed between the Ki estimated by both Hunter and our methods and the Ki estimated by LR: R2=0.87, R2=0.86, respectively. A good correlation (R2=0.83) was observed between SUV and Ki estimated by LR., Conclusions: These three simplified methods represent a valid alternative to the more invasive and complex full kinetic analysis. Their "pros" are: the non-invasiveness, the feasibility, the good correlation with the golden standard; their "cons" is that full kinetic analysis provides highest accuracy in Ki determination. Therefore, in clinical oncology routine, the nuclear physicians can choose among different simplified methods especially for monitoring the response to treatment, for tumour grading, and for prognostic stratification, letting the full kinetic analysis to specific centre/studies.

Study Design: Retrospective study., Objective: To evaluate, in a pediatric population, F-Fluoro-deoxy-glucose (F-FDG) metabolic activity of normal spinal cord and to assess the correlation with demographic, clinical, and environmental variables., Summary of Background Data: F-FDG uptake of normal spinal cord is variable in children. The knowledge of physiological metabolism of spinal cord is essential to distinguish normal from pathological findings by positron emission tomography-computed tomography (PET-CT)., Methods: We retrospectively evaluated F-FDG positron emission tomography-computed tomography scans from a total of 167 pediatric patients (97 males; 3.9-18.9 yr) divided into 4 age groups (0-4.9 yr, 5-9.9 yr, 10-14.9 yr, and 15-18.9 yr), excluding those submitted to previous or recent therapeutic procedures influencing spinal cord metabolism or with central nervous system diseases. Spinal cord was divided into 3 levels (C1-C7; D1-D6; and D7-L1), and maximum standardized uptake value (SUVmax) of each cord level was measured. Correlations between SUVmax and spinal cord level, age, body weight, sex, type of disease, and season were statistically assessed., Results: Median SUVmax was similar and significantly (P < 0.01) higher at C1-C7 and D7-L1 levels than at D1-D6 level and it significantly (P < 0.01) increased with age in all spinal cord levels. A positive and significant association between SUVmax and body weight, female sex, and Hodgkin lymphoma was found. No significant association with season was observed. By multivariate analysis, only weight and female sex remained significant., Conclusion: Knowledge of physiological F-FDG spinal cord activity in children is essential for a correct interpretation of positron emission tomography-computed tomography, especially in oncologic pediatric patients to avoid potential pitfalls., Level of Evidence: N/A.

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 (18)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 (18)F-FDG PET/CT, and surgery., Results: Of the 26 ocular lesions, 23 showed (18)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 (18)F-FDG in evaluating prognosis.

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

Radioiodinated metaiodobenzylguanidine (MIBG) was developed in the late 1970's, at the Michigan University Medical Center, for imaging of the adrenal medulla and its diseases. Soon after, MIBG was shown to depict a wide range of tumors of neural crest origin other than pheochromocytomas/paragangliomas (Pheo/PGL) with the result that its use rapidly spread to many countries. After more than 30 years of clinical application, MIBG continues to be the most widespread radiopharmaceutical for the functional imaging of Pheo/PGL in spite of the emergent role of PET agents for detection of these tumors. In this paper we review the evolution in the use of MIBG over more than 30 years of experimental and clinical applications, with particular focus on the uptake mechanisms, pharmacokinetics, biodistribution and drug interaction as well as on clinical studies in Pheo/PGL also in comparison to other gamma-emitters tracers and PET radiopharmaceuticals.

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.

Background: 18F-fluoro-deoxy-glucose (18 F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18 F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm., Case Presentation: We report five cases of oncologic patients showing focal lung 18 F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18 F-FDG false-positive and false-negative results in the pulmonary parenchyma.In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18 F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT., Conclusion: In all five oncologic patients, 18 F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18 F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT.

Positron emission tomography (PET) is widely used in the diagnostic evaluation and staging of different malignant tumors. The role of PET/computed tomographic scan in detecting distant metastases in the workup of Ewing sarcoma in children or young adults is less well defined. We report a case of a boy affected by a metastatic Ewing sarcoma with cardiac asymptomatic metastasis detected by F-FDG PET/computed tomography.

Background: The prognosis of patients with advanced neuroblastoma (NB) remains poor. Major and early responses have an important bearing on treatment outcome. Iodine-131-metaiodobenzylguanidine (¹³¹I-MIBG) has the potential to deliver large doses of radiation specifically to NB cells. We evaluated the toxicity of, and response to, a novel induction regimen that included ¹³¹I-MIBG combined with cisplatin, cyclophosphamide, etoposide, vincristine, and doxorubicin., Procedure: Thirteen children over 1 year of age with advanced NB at diagnosis were investigated extensively. ¹³¹I-MIBG was administered on day 10; this was preceded by chemotherapy in the five patients in group 1 (described in our previous study), and both preceded and followed by chemotherapy in the eight patients in group 2. The final induction regimen (used for group 2) lasted 1 month. Evaluation was performed 40 days after the start of treatment., Results: In both groups 1 and 2, the extent of hematologic toxicity, which was the only side effect, was similar to that seen with chemotherapy alone. Doses of ¹³¹I-MIBG as high as 16.6 mCi/kg showed no evidence of toxicity, even in patients with extensive bone marrow infiltration. Overall, we recorded two patients with a complete response (CR), six very good partial responses (VGPR), four partial responses (PR), and one mixed response (MR). In group 2, CR/VGPR were observed in patients treated with higher doses of ¹³¹I-MIBG., Conclusions: The results of this pilot study show that ¹³¹I-MIBG, in combination with chemotherapy, appears to play an important role in a new and effective induction regimen for advanced NB., (Copyright © 2011 Wiley-Liss, Inc.)

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.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating in the parafollicular cells (C cells) of the thyroid and secretes both calcitonin and carcino-embryonic antigen (CEA). Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary thyroid nodule; the diagnosis can be made preoperatively by fine-needle aspiration or by calcitonin assay, though it is usually established at the time of surgery. In the diagnostic assessment of MTC, nuclear medicine imaging provides its contribution mainly in the post-operative work-up to detect residual/recurrent tumor. For such purpose a number of radiopharmaceuticals, which take advantage of the specific expression of receptors (the somatostatin analogue (111)In-octreotide), hormone transporters (radiolabelled MIBG) or molecular targets (radiolabelled anti-CEA monoclonal antibodies) by MTC lesions are available; these tracers may be used also for the palliative treatment of advanced MTC. Interesting perspectives for MTC imaging are offered by PET radiopharmaceuticals.

Unilateral hydronephrosis due to obstruction of the uretero-pelvic junction is one of the most common indications for scintigraphic evaluation of the kidneys in the pediatric patient. In these cases, dynamic renal scintigraphy-both standard and after diuretic administration--is a simple and well-established procedure, allowing demonstration of structural and functional abnormalities of the involved kidney, with relatively low radiation dose to the child. Scintigraphic procedures allow the differential diagnosis between obstructive and non obstructive causes as well as an estimation of renal function of the hydronephrotic kidney providing indication for a conservative or a surgical approach.

Simple Summary: Among head–neck tumors, squamous cell carcinoma is the most frequent histotype and includes a range of malignancies with different sites of origin as well as different therapeutic strategies and clinical outcomes. In daily practice, patients with head–neck squamous cell carcinoma are seen in various clinical settings, requiring a multidisciplinary approach to therapeutic decisions and clinical care. 18F-FDG PET/CT plays a well-defined role in the management of these tumors for pre-treatment staging and radiotherapy planning as well as treatment-response assessment and post-therapy follow-up. This paper is an overview of the standard use of 18F-FDG PET/CT in the various clinical scenarios of head–neck squamous cell carcinoma. Also, emerging applications will be reviewed, including the use of radiopharmaceuticals other than 18F-FDG, PET/MRI implementation in clinical practice, and the use of radiomics and machine learning. This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with locally advanced cervical cancer, the availability of imaging techniques for accurately defining the residual tumor would be clinically relevant for selecting patients who could be offered a more tailored surgery. The novelty of this prospective study is the development of multiparametric predictive models of histopathological response using a unique data set with three imaging modalities (transvaginal ultrasound, magnetic resonance (MRI) and 18F-FDG-PET/CT) evaluated at three time points ("baseline", two ("early") and five ("final") weeks after treatment). In a cohort of 88 patients, the predictive models retrieved integrating morphometric, vascular, perfusion and metabolic parameters, demonstrated that two imaging approaches (MRI and PET/CT at "final" evaluation or PET/CT at "baseline" and "final" evaluation) are sufficient to identify possible residual disease after chemotherapy. These findings could be useful in selecting patients with residual disease, helping clinicians to tailor the radicality of the surgical approach. Purpose: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. Methods: Patients with histologically proven LACC, stage IB2–IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment ("baseline", "early" and "final", respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. Results: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT "baseline" and "final" examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at "final" evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71–0.90) and 0.81 (0.72–0.90), respectively). Conclusion: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable. [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. To perform an overview about the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using different radiopharmaceuticals in recurrent medullary thyroid carcinoma (MTC) based on biochemical findings (increased tumor marker levels after primary surgery). Methods. A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through February 2012 regarding PET or PET/CT in patients with recurrent MTC was performed. Results. Twenty-nine studies comprising 714 patients with suspected recurrent MTC were retrieved. Twentyseven articles evaluated the role of fluorine-18-fluorodeoxyglucose (FDG) PET or PET/CT in recurrent MTC with conflicting results. Diagnostic accuracy of FDG-PET and PET/CT increased in MTC patients with higher calcitonin and carcinoembryonic antigen values, suggesting that these imaging methods could be very useful in patients with more advanced and aggressive disease. Eight articles evaluated the role of fluorine-18-dihydroxyphenylalanine (FDOPA) PET or PET/CT in recurrent MTC reporting promising results. Overall, FDOPA seems to be superior but complementary compared to FDG in detecting recurrent MTC. Few studies evaluating other PET tracers are also discussed. Conclusions. PET radiopharmaceuticals reflect differentmetabolic pathways in MTC. FDOPA seems to be the most useful PET tracer in detecting recurrentMTC based on rising levels of tumor markers. FDG may complement FDOPA in patients with more aggressive MTC. [ABSTRACT FROM AUTHOR]