The evolution of PET imaging in renal, bladder, upper urinary tract urothelial, testicular and penile carcinoma - Today's impact, tomorrow's potential.

INTRODUCTION: The advancement of hybrid PET/CT or PET/MRI imaging for non-prostate genitourinary cancers has not experienced the rapid progress of prostate cancer. Nevertheless, these neoplasms are aggressive and reliable imaging plays a pivotal role in enhancing patients' quality of life and prognosis. AREAS COVERED: the main evidence regarding [18F]FDG and non-[18F]FDG PET/CT or PET/MRI in non-prostate uro-oncological malignancies are summarized and discussed. Moreover, potential future directions concerning PET imaging in these neoplasms are debated, with the aim to stimulate future research projects covering these fields. EXPERT OPINION: In Renal Cell Carcinoma (RCC), [18F]FDG PET/CT demonstrates varying efficacy in staging, restaging, and prognostic stratification, but PSMA PET/CT is emerging as a potential game-changer, particularly in advanced, high-grade aggressive clear cell RCC. [18F]FDG PET/CT may see an increased use in N and M-staging of bladder cancer, as well as for detecting recurrence and response to neoadjuvant chemotherapy. Preliminary data regarding [68Ga]-FAPI also looks promising in this context. [18F]FDG PET/MRI could be useful for the T-staging of bladder cancer, while upper tract urothelial carcinoma still lacks of molecular imaging literature reports. In testicular and penile cancer [18F]FDG PET/CT has demonstrated its usefulness in several clinical settings, although experiences with non-[18F]FDG radiotracers are lacking.

Cavernous Hepatic Hemangioma at 18F-Choline Positron Emission Tomography-Computed Tomography: Be Aware of the Pitfall.

We report a case of a patient performing a positron emission tomography-computed tomography (PET-CT) scan with [18F]F-Choline for biochemical relapse (Prostate specific antigen (PSA) 1.2 ng/ml) of prostate cancer. Two large areas of focal uptake with a cold core within the liver were observed. A contrast-enhanced ultrasound scan performed after the PET scan characterized these lesions as cavernous hepatic hemangiomas, and therefore, a biopsy was not performed; 3 years of follow-up and PET and MRI finding stability confirmed the benignity of their nature.

Reorganization of a Nuclear Medicine Department in Northern Italy During a 2-Month Lockdown for COVID-19 Pandemic.

Coronavirus disease (COVID-19) outbreak has profoundly changed the organization of hospital activities. We present our experience of reorganization of a nuclear medicine service settled in Northern Italy during the pandemic period of March and April 2020 characterized a government-mandated lockdown. Our service remained open during the whole period, performing approximately 80% of the routine practice, while maintaining it COVID-free despite the geographical context characterized by a high risk of infection. Reorganization involved all aspects of a nuclear medicine department, following local, national, and international guidelines for prioritizing patients, telephone and physical triages, deployment of appropriate personal protective equipment, social distancing, and logistic changes for scheduling examinations and disinfection procedures. All staff remained COVID-19-negative despite the unintentional admission of 4 patients who later turned out to be positive for the severe acute respiratory syndrome coronavirus 2. These adopted measures would serve as the basis for safe nuclear medicine services in the post-lockdown phase.

A new mobile self-dispensing and administering system for 18F-FDG: evaluation of operator dose reduction.

PURPOSE: Recently new mobile systems for dispensing positron emitters have been produced, designed to guarantee dispensing cycles in an aseptic environment. The aim of the present work was to assess the advantage of one of these systems in radiation protection of operators in clinical settings. METHODS: Recently, in our centre the new self-dispensing system named KARL100 by Tema Sinergie was adopted for 18F-FDG radiopharmaceuticals. The system is associated with an automatic Rad-inject infuser. The system that was previously used was a fixed isolator NMC DSI (Tema Sinergie), equipped with a µDDS-An activity fractioning system, together with a pneumatic post for the syringe delivery. The dosimetric evaluations on both systems were carried out through environmental measurements with an ionisation chamber and with the use of personal dosimeters. RESULTS: The operations of preparation and administration of 18F-FDG dose to the patient, with the use of Karl100 + RadInject, involve exposures much lower than those obtained by the fixed isolator. The average body exposure of the technician was reduced by 31%, and for the physician by 77%. On the extremities, the equivalent dose to the hands of the technician was reduced by 78%, and for the physician by 96%. Also the additional dosimeters worn by the technician confirmed the estimated environmental assessments. CONCLUSIONS: The exposures of the working personnel were significantly reduced with the introduction of the new KARL100 system.

How to harmonize SUVs obtained by hybrid PET/CT scanners with and without point spread function correction.

State of the art point-spread function (PSF) corrections implemented in positron emission tomography/computed tomography (PET/CT) reconstruction improved image quality and diagnostic performance but caused an increase in the standardized uptake value (SUV) compared to a conventional OSEM reconstruction system. The EANM suggested one produce two reconstructions, one optimised for maximum lesion detection and one for semi-quantitative analysis. In this work we investigated an alternative methodology, using a single reconstruction data set together with a post-reconstruction algorithm for SUV harmonization. Data acquisition was performed on a Siemens Biograph mCT system equipped with lutetium oxyorthosilicat crystals, PSF and time-of-flight algorithms and on a General Electric Discovery STE system equipped with BGO crystals. Both a EANM double reconstruction method and a dedicated post-reconstruction algorithm (marketed as EQ-filter) were tested to harmonize the quantitative values of the two PET/CT scanners. For phantom measurements we used a NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small spheres (lesion to background ratios of 8:1 and 4:1). Several different reconstruction settings were tested in order to provide a general methodology. Data obtained by phantom measurements were validated on seven oncologic patients who performed a one-bed extra acquisition on a different scanner. The evaluation regarded 39 small lesions (diameters: 0.3-2.6 cm) and was performed by two experienced nuclear medicine physicians. The SUV recoveries measured with the PSF reconstruction exceeded those obtained by the OSEM reconstruction with deviations ranging from 16% to 150%. These discrepancies resulted below 7% applying the optimized value of the EQ.filter or the double-reconstruction methods. For each reconstruction setting the optimal value of the EQ.filter was identified in order to minimize these discrepancies. Patient data, analyzed by Wilcoxon statistical test, confirmed and validated phantom measurements. EQ.filter can harmonize SUV values between different PET/CT scanners using a single reconstruction optimized to maximum lesion detectability. In this way, the second reconstruction proposed by EANM/EARL is avoided.

18F-FDG PET/CT of Generalized Arteritis.

A 75-year-old man presented with significant weight loss, persistent cough, single episode of frontotemporal pulsatile headache, and leg weakness. A paraneoplastic syndrome was suspected, and F-FDG PET/CT was performed. Diffuse, moderate-to-intense tracer symmetrical uptake of many large and medium arteries was unexpectedly noted. The peculiarity of this case is the extensive involvement of both large and medium head and neck and extremity vessels, whereas the aorta was relatively spared.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Optimized protocol for (18)F-choline PET/CT in patients with biochemically relapsed prostate cancer: experiences on 250 consecutive cases.

PURPOSE: We review acquisition F-choline PET/CT methodology, evaluate a new F-choline acquisition protocol for prostate cancer (PC), and propose a standardized acquisition protocol on F-choline in PC patients. MATERIALS: Two hundred fifty consecutive PC patients (mean age 72 years, mean PSA 7.9 ng/mL) were prospectively evaluated with F-choline PET/CT. An early scan of the pelvis (1 bed position of 4 minutes) was followed by a whole-body scan at 1 hour. Early and 1 delayed hour images of the pelvis were compared. RESULTS: Twenty-one percent of patients (n = 57) with positive F-choline demonstrated abnormal local uptake; 18% of patients (n = 45) showed distant localization only; 23% of patients (n = 53) had both local and distant localization; 38% of patients (n = 38) did not show any pathological uptake. All early images showed absence of radioactive urine in ureters, bladder, or urethra with satisfactory visualization of the prostatic region. Considering the group of patients with local uptake only, the prostatic region uptake, confirmed by late images, was better visualized in the early phase in 32/57 cases (SUVmax 12.4 ± 3.2 vs. 7.3 ± 5.2, P <0.01). Instead distant lesions were visualized on both early and late images with similar uptakes values (SUVmax 9.8 ± 4.1 vs. 10.3 ± 4.5, P = N.S.). CONCLUSION: Early F-choline images improve pelvic prostate cancer lesion clarity. All pathologic pelvic deposits (prostate, lymph nodes, bone) were visualized both in the early and late images.

18F-FDG PET/CT lung 'focalities' without coregistered CT findings: an interpretative clinical dilemma.

AIM: The aim of the study was to assess the prevalence of focal fluorine-18 fluorodeoxyglucose (18F-FDG) activity in the lungs using 18F-FDG PET/computed tomography (CT) without matching CT findings. MATERIALS AND METHODS: A total of 10,500 consecutive 18F-FDG PET/CT records over 4 years were reviewed for focal incongruence between PET and CT, potentially indicating an artifact 18F-FDG (2.2 MBq/kg) was injected through a butterfly needle, followed by a 10 ml saline flush. Non-contrast-enhanced low-dose CT (140 kV and 40-80 mA) was coregistrated with PET. RESULTS: Sixteen patients (12 men and four women; mean age 63 years, range 44-83) had focal pulmonary areas of high 18F-FDG activity [mean maximum standardized uptake value (SUV max) 15.8; range 3.5-81.0], typically peripheral, with a mean maximum diameter of 1.3 cm (range 0.5-2.2 cm) on PET. 18F-FDG focality was singular in 14 patients, whereas two patients had two foci each. None had corresponding CT abnormalities. Identification of these 'focalities' during the acquisition phase led to late respiratory gated thoracic PET acquisitions in eight patients at 2 h with no significant changes in the location or size of the 'focalities'. Five PET/CTs repeated at 48 h did not confirm the 'focalities'. Five had negative follow-up contrast-enhanced CT. 18F-FDG-positive 'focalities' at PET/CT without anatomical correlation findings were considered as 'artefactual accumulation' of the tracer. CONCLUSION: In the absence of morphological abnormality, focal pulmonary 18F-FDG activity is very rare (1.5 cases/1000 PET scans) but potentially very 'dangerous'. Artefact identification during acquisition can lead to late respiratory gated images for more confident interpretation, avoiding erroneous reports or further imaging procedures.

Role of 18F-FDG PET/CT in the carcinoma of the uterus: a review of literature.

In the present review we reported the value of 18F-fluorodeoxyglucose (FDG) PET/CT in face of uterine cancer, in terms of sensitivity, specificity and accuracy. Moreover, we made a comparison with the other imaging techniques currently used to evacuate these tumors including contrast-enhanced CT, contrast enhanced-MRI and transvaginal ultrasonography. FDG PET/CT has been reported to be of particular value in detecting occult metastatic lesions, in prediction of response to treatment and as a prognostic factor.

New acquisition protocol of 18F-choline PET/CT in prostate cancer patients: review of the literature about methodology and proposal of standardization.

PURPOSE: (1) To evaluate a new acquisition protocol of (18)F-choline (FCH) PET/CT for prostate cancer patients (PC), (2) to review acquisition (18)F-choline PET/CT methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT in PC patients. MATERIALS: 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings. RESULTS: The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30) of cases. Other pelvic pathologic findings (bone and lymph nodes) were visualized in both early and late images. CONCLUSION: Early (18)F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone) were visualized in both early and late images.

Non-Alzheimer types of neurodegenerative dementia: clinical and 18F-FDG-PET/CT pictures.

Primary degenerative dementia syndromes are an increasingly relevant problem worldwide because of the progressive aging of the population. Their diagnosis is often a challenge for clinicians and, even in the best cases, only a possible or probable diagnosis can be reached. Molecular neuroimaging techniques can be very useful in dementia patients, especially for obtaining a diagnosis in the early stage of disease. The most diffuse and widely available nuclear medicine method for neurological studies is F-fluoro-deoxy-glucose (F-FDG)-PET, which allows the quantification of glucose gray matter metabolism and helps visualize typical, adequately specific, patterns for many kinds of degenerative dementia, not only for the well-known and well-studied Alzheimer's disease. This paper aims to describe the clinical and F-FDG-PET profiles of the principal non-Alzheimer type of degenerative dementias.

Pretherapeutic dosimetry in patients affected by metastatic thyroid cancer using 124I PET/CT sequential scans for 131I treatment planning.

PURPOSE: This study evaluates the use of sequential I PET/CT for predicting absorbed doses to metastatic lesions in patients with differentiated thyroid cancer undergoing I therapy. METHODS: From July 2011 until July 2013, 30 patients with metastatic differentiated thyroid cancer were enrolled. Each participant underwent PET/CT at 4, 24, 48, and 72 hours with 74 MBq of I. Blood samples and whole-body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT were used to evaluate tumor doses with medical internal radiation dose formalism and spheres modeling. Mean administered I therapeutic dose was 5994 MBq (range, 1953-11,455 MBq). RESULTS: I PET/CT demonstrated all lesions detected by posttherapy I whole-body scans. Mean dose rates for blood, red marrow, and lesions were as follows: 0.07 ± 0.02 mGy/MBq, 0.05 ± 0.02 mGy/MBq, and 46.5 ± 117 mGy/MBq, respectively. Despite the high level of thyroid-stimulating hormone and CT detectable lesions, 15 of 30 patients did not show any abnormal I uptake. CONCLUSIONS: The quantitative value of I PET/CT allows simple and accurate evaluation of lesion dosimetry following medical internal radiation dose formalism. Negative I PET/CT predicts absence of iodine avidity, potentially allowing avoidance of therapeutically ineffective I administration.

18F-FDG PET/CT in tumefactive multiple sclerosis.

A 35-year-old man underwent contrast-enhanced MRI and F-FDG PET/CT for acute peripheral paresthesia, vision loss, muscle weakness, and difficulty walking. T2-weighted MRI demonstrated multiple bright periventricular supratentorial and infratentorial white matter lesions, including 2 with nodularity. Both nodular lesions showed moderate focal FDG uptake (SUVmax, 6.9 in both cases). Cerebrospinal fluid analysis showed increased levels of immunocytes and oligoclonal antibody bands. A diagnosis of acute onset tumefactive multiple sclerosis was made.

Are PREDIST criteria better than PERCIST criteria as a PET predictor of preoperative treatment response in rectal cancer?

Fluorine-18-fluorodeoxyglucose PET/CT is an accurate tool for predicting the response to preoperative chemoradiotherapy in locally advanced rectal cancer patients. The need for standardization has contributed to the development of various criteria for harmonizing PET response. The novel proposed set of criteria called PET Residual Disease in Solid Tumor (PREDIST) seems to better distinguish between responder and nonresponder patients to chemoradiotherapy compared with the PET Response Criteria in Solid Tumors criteria.

Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

PURPOSE: To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. MATERIALS AND METHODS: We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. RESULTS: Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. CONCLUSION: Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.

Restaging clear cell renal carcinoma with 18F-FDG PET/CT.

AIM: The aim of our retrospective study was to assess the usefulness of F-FDG PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Sixty-nine patients (median age = 62 years; range = 36-86 years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13 patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20 patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the disease after nephrectomy for clinical or radiological suspicion of metastases. Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake, equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients). RESULTS: F-FDG PET/CT was positive in 42 patients and negative in 27 patients. Sixteen patients presented single lesions and 26 patients presented multiple localizations of the disease. On a patient basis, 40 patients resulted true positive, 2 patient false positive, 23 patients true negative, and 4 patients false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive patients of which 112 resulted to be true positive. FDG uptake of the true positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and finally faint in 12 lesions. CONCLUSIONS: F-FDG PET/CT demonstrated a good sensitivity in the restaging of clear cell RCC. Most of the lesions showed intense activity. According to our results, it seems that the use of F-FDG PET/CT in the restaging of RCC is feasible because the number of false-negative cases is limited.

Management of epithelial ovarian cancer from diagnosis to restaging: an overview of the role of imaging techniques with particular regard to the contribution of 18F-FDG PET/CT.

Epithelial ovarian carcinoma is a major form of cancer affecting women in the western world. The silent nature of this disease results in late presentation at an advanced stage in many patients. It is therefore important to assess the role of imaging techniques in the management of these patients. This article presents a review of the literature on the role of (18)F-FDG-PET/CT in the different stages of management of epithelial ovarian cancer. Moreover, a comparison with other imaging techniques has been made and the relationship between (18)F-PET/CT and the assay of serum CA-125 levels has been discussed.

Molecular imaging of pulmonary nodules.

OBJECTIVE: Lung nodules can be benign or malignant, reflecting many possible causes, ranging from inflammatory and infectious processes to neoplasms. Incidental detection on chest x-ray or thoracic CT often requires further evaluation by imaging or invasive procedures. CONCLUSION: Currently, 18F-FDG PET/CT offers both anatomic and metabolic characterization of lung nodules. Fluorine-18-thymidine, 11C-methionine, 68Ga-DOTA-somatostatin analogs, and 18F-dihydroxyphenylalanine may offer additional molecular information useful for diagnosis and treatment planning.