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Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LC

The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today's nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs opens in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics-that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.

Liver magnetic resonance imaging (MRI) utilizing hepatocyte-specific contrast agent and diffusion-weighted imaging (DWI) is currently used to properly stage colorectal liver metastases (CRLM) in patients candidate to liver surgery. However, the added value of liver MRI in choosing the treatment strategy in resectable CRLM over computed tomography (CT)-scan is not clear.This is a prospective monocentric collection of consecutive cases of patients with CRLM conceived with the aim to assess the added value of liver MRI in changing the initial treatment strategy planned according to CT-scan. Potential changes in the initially planned strategy were defined as: - from upfront surgery to perioperative chemotherapy (fluoropyrimidine and oxaliplatin) - from upfront surgery to first-line systemic therapy (doublet or triplet plus a biological agent) - from perioperative chemotherapy to first-line systemic therapy. Hypothesising that MRI may induce a change in the choice of the treatment strategy in the 20% of cases (alternative hypothesis), against a null hypothesis of 5%, with one-tailed alpha and beta errors of 0.05 and 0.20 respectively, 27 patients were needed. The added value of liver MRI would have been considered clinically meaningful if at least 4 changes in the treatment strategy were observed.Among 27 enrolled patients, upfront surgery and perioperative chemotherapy strategies were chosen in 17 (63%) and 10 (37%) cases, respectively, based on CT-scan. After liver MRI, additional liver lesions were found in 8 patients (30%) and the initial strategy was changed in 7 patients (26%) (4 initially deemed candidate to upfront surgery and 3 initially sent to perioperative chemotherapy) that were treated with first-line systemic therapy.Our results support the indication of the current guidelines on the routine use of liver MRI in the initial workup of patients with resectable CRLM with an MRI-driven changes of initial treatment plan in a relevant percentage of cases.

Background/aim To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. Patients and methods This retrospective investigation analyzed 67 patients at first relapse. Results At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. Conclusion Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

Context 18F-fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography ([18F]-FDG-PET/CT)–positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. Objective We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. Methods Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. Results Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). Conclusions Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Aim To assess the correlation between contrast-enhanced computed tomography (CE-CT) and positron-emission tomography (PET)/CT results and surgical and pathological findings in patients with recurrent platinum-sensitive ovarian cancer who underwent secondary cytoreduction. Patients and methods 18F-fluorodeoxyglucose (18F-FDG) PET/CT with/without CE-CT were performed before 56 cytoreductive surgeries in 49 patients with suspicious recurrent ovarian cancer. Results 18F-FDG PET/CT showed higher sensitivity and diagnostic accuracy compared with CE-CT for both the whole series (100% versus 90.6%, respectively, and 97.8% versus 85.3%), and the 24 cases in which both examinations were performed (100% versus 87.0% and, respectively, 95.8% versus 83.3%). The addition of CE-CT to 18F-FDG PET/CT did not improve its diagnostic reliability. Conclusion 18F-FDG PET/CT appears to be the more reliable imaging technique for the evaluation of patients with suspicious recurrent ovarian cancer, and for the selection of those more suitable for secondary cytoreductive surgery.

Renal cell carcinoma (RCC) has a high metastatic potential, and most commonly metastasizes via the bloodstream, although lymphatic metastases also occur. RCC is well-known for its propensity to metastasize to unusual sites, and late metastasis, even after a number of years, is common. The occurrence of RCC metastasis to the head and neck region is uncommon, and occurs primarily in the thyroid gland and in patients with widespread dissemination. Involvement of the parathyroid gland in metastatic carcinoma is extremely rare. In the present report, a case of metastasis confined to the parathyroid gland is described, likely with intrathyroidal localization, arising from a RCC that occurred 16 years after nephrectomy. A 66-year-old man was referred to the Department of Surgery of the University Hospital of Pisa (Pisa, Italy) with a preoperative fine-needle aspiration diagnosis of a follicular lesion in the context of nodular goiter of the thyroid gland. The previous medical history of the patient included a right nephrectomy for the treatment of clear cell RCC in February 1997. No other distant metastases were identified as of the latest follow-up in March 2014. At the time of thyroid surgery, the thyroid and parathyroid function tests were normal. The gross appearance of the surgical specimen was a multinodular goiter with a solid nodule measuring 33 mm on the left lobe of the thyroid gland. Microscopic examination revealed a completely encapsulated lesion consisting of clear cells arranged in a solid pattern and intermixed with fragments of parathyroid tissue. Following immunohistochemical examination, the clear cell lesion was negative for thyroid transcription factor-1 and thyroglobulin and strongly positive for epithelial membrane antigen, cluster of differentiation 10 and vimentin. To the best of our knowledge, this is the second case of metastasis to the parathyroid gland from a RCC reported in the literature.

Because of unsatisfactory accuracy of preoperative imaging and/or of mediastinoscopy, current guidelines recommend routine dissection of mediastinal lymph nodes for patients with operable non-small cell lung cancer (NSCLC). However, at final histopathology this surgical procedure, which is performed mostly for staging purposes and implies a non-negligible rate of severe complications, turns out to be unnecessary in a quite large proportion of patients with early NSCLC. These considerations explain the interest in exploring the potential of sentinel lymph node biopsy (SLNB) in patients with NSCLC, an approach based on the same rationale that has led to establish SLNB as the standard of care in patients with cutaneous melanoma or breast cancer (especially if performed with intraoperative gamma probe guidance after injection at the tumor site of a radiolabeled agent for lymphatic mapping). However, in the case of NSCLC objective anatomic difficulties prevent the possibility to access the primary tumor for injection of the lymphatic mapping agent through an easy and minimally invasive administration route and with adequate timing so to allow for adequate preoperative imaging. Although different methodological approaches have been explored to overcome these difficulties, the clinical evidence so far acquired does not justify the use of SLNB as a routine clinical procedure to stage the tumor status of mediastinal lymph nodes in patients with NSCLC. Nonetheless, the search is continuing for the optimal combination of techniques to optimize and validate the SLNB approach for NSCLC; promising perspectives in this regard include a combination of multimodal techniques, for instance intraoperative gamma probe guidance combined with detection of either an optical and/or a magnetic signal.

Adrenal glands are two organs of the endocrine system that secrete different types of hormones. They are located in the retroperitoneal space, surrounded by a thick fibrous capsule, placed immediately below the diaphragm, superiorly and medially to the kidneys, between the 12th thoracic and the 1st lumbar vertebra. They have a cone shape with an inferior base, a weight of about 8 g, and sizes of about 2–3 cm in width and 4–6 cm in length. They are richly vascularized, innervated by the autonomous system, mainly through the adrenal plexus. Each adrenal consists of two distinct parts: a peripheral part, called adrenal cortex, and a central part, called adrenal medulla.

Neuroendocrine tumors (NETs) constitute a heterogeneous group of rare tumors that arise from cells of the neuroendocrine system. The term “neuroendocrine” relates to the ability of these cells to produce and store amines and peptide hormones produced by both the endocrine system and the nervous systems: gastrin, insulin, serotonin, somatostatin, glucagon, pancreatic polypeptide, vasoactive intestinal peptide (VIP), catecholamines, ACTH, GH, prolactin, FSH, LH, TSH, and PTH. Although NETs differ widely in their biology and clinical presentation, they share the capability to produce certain biological compounds (chromogranins and synaptophysin) that are considered specific markers of neuroendocrine cells [1].

The thyroid gland is a butterfly-shaped organ located anteriorly to the trachea at the level of the second and third tracheal rings. It consists of two lobes connected by the isthmus in the midline. Anteriorly, its surface is convex; posteriorly, it is concave. The gland’s upper extremities are known as the upper poles. Similarly, the lower extremities of the lateral lobes are known as the lower poles (or base of the lobe). The weight of the thyroid of the normal non-goitrous adult is 6–20 g depending on the body size and iodine supply. From upper pole to base, the thyroid lobes usually measure 4 cm. Their width is 15–20 mm, and their thickness is 20–39 mm. The isthmus is 12–15 mm high, lies across the trachea anteriorly just below the level of the cricoid cartilage, and connects the two lobes. The shape and attachments of the organ and its relationship to the trachea are important in examination and diagnosis and from the point of view of pressure symptoms.

Therapeutic radiopharmaceuticals exert their radiobiological action through the emission of electrically charged particles (α++ particles, β− particles, Auger electrons) that deposit their energy within a limited range in tissue—from fraction of a micrometer to a few millimeters at most. The goal of radionuclide therapy is to cause radiobiological effect with irreversible damage to cell DNA, resulting in cell death. The radionuclides are linked to carrier molecules capable of selectively transporting the radiotracers to the target tissues (in the majority of cases it is used for oncological purpose). At the moment the main indications of radionuclides therapy include treatment of malignant or benign thyroid disease, neural crest-derived tumors, neuroendocrine tumors, Non Hodgkin’s lymphoma, metastatic bone disease and intraarterial therapy of liver tumors.

Since its earliest introduction in the late 1950s [1], the Anger camera is still the most widely diffused system for clinical radionuclide imaging. This success relies mainly on the simplicity of the principle for determining position of the γ-ray interaction with the scintillation crystal. Furthermore, continuing technological advances in growing large-volume scintillation NaI(Tl) crystals and in producing standard photomultiplier tubes (PMTs) have led to develop cost-effective detectors, with an area sufficiently large for human studies. Also the intrinsic spatial resolution is still well optimized to image large and deep organs, where spatial resolution is dictated by the collimator properties. On the other hand, the large size and weight and the extension of a “dead” zone at the edges of the Anger camera make it difficult to position the camera for some studies, e.g., when imaging a small organ [2].

The kidneys are located in the retroperitoneal space at the sides of the psoas muscle (D11-L3 tract), about 7 cm in depth from the posterior abdominal wall. The left kidney is typically somewhat more superior in position than the right kidney. The upper poles are normally oriented more medially and posteriorly than the lower poles. The medial margin of each kidney is marked by a deep fissure, known as the renal hilum that acts as a gateway to the kidney.

Although several designs and operational differences exist among the various gamma camera devices on the market, it is well known that every gamma camera, considered as a whole as crystal-photomultiplier-electronic system, invariably generates distortions that must be minimized and corrected in order to obtain images with good spatial resolution and contrast. Therefore, several correction maps and key parameters are commonly included in the system as a default preset configuration and then applied in real-time mode when planar or SPECT images are acquired.

The liver can be the site of both primary and metastatic malignancies. Besides hepatocellular carcinoma (HCC, ranking fifth among the most common malignancies worldwide) [1], different solid tumors primarily arising in other tissues/organs, most importantly colorectal cancer (CRC), frequently give rise to metastases in the liver [2].

Molecular imaging, which is based on the ability to image alterations underlying diseases at the subcellular, molecular level, has the potential not only to detect disease early on—before anatomic abnormalities become obvious at morphologic imaging—but also to monitor the efficacy of treatment(s) before anatomic changes take place in response to therapy. These features imply the possibility to detect/diagnose disease early and accurately and to predict response to therapy early on during treatment, therefore to facilitate implementation in the medical practice of a true personalized medicine tailored to the needs/characteristics of the individual patient.

Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor­betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.

We investigated the striatal and extrastriatal DAT availability (SPM8) by [123I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p

The purpose of this review is to provide a reappraisal of the diagnostic imaging procedures for thyroid carcinoma in pediatric patients, including thyroid ultrasound (US), ultrasound-guided fine-needle aspiration biopsy (FNAB), scintigraphy, radiological techniques (CT, MR), and PET/CT. The most frequent indication for thyroid imaging is characterization of a palpable mass in the neck or thyroid gland. Thyroid US is a first-line examination for visualizing the thyroid gland as it provides anatomic and perfusion information; on the other hand, scintigraphy mostly provides functional information but combined with some anatomic information as well. CT and MRI have a supplemental role in these patients. Furthermore, with the introduction of PET/CT and the development of new imaging agents, nuclear medicine plays an important role in different phases of neoplastic disease in terms of both staging and evaluation of response to medical/surgical treatments.

OBJECTIVE. MRI and 99mTc-sestamibi scintigraphy are used to estimate bone marrow infiltration in patients with Gaucher disease (GD), but comparison of data obtained at different institutions is difficult because different scores are employed for semiquantitative assessment. We developed normalized scores for comparing data both within a single method (MRI) and between different methods (MRI versus scintigraphy). MATERIALS AND METHODS. We evaluated 51 patients with type 1 GD (26 women, 25 men; mean age ± SD, 36.3 ± 10.9 years old). T1- and T2-weighted turbo spin-echo sequences at 1.5 T served to derive the bone marrow burden score (0-16), the vertebra-disk ratio (VDR), the Terk score (0-3), and the Spanish-MRI score (S-MRI, 0-24). Scintigraphy was scored between 0 and 8. Each score was normalized into four categories: 0 = normal, 1 = mild, 2 = intermediate, 3 = severe involvement. Interobserver and intraobserver agreements were evaluated by kappa statistics; nonparametric statistics with Bonferroni correction assessed correlations among the various original and normalized scores. RESULTS. Interobserver agreement was excellent for the original scores (κ = 0.730- 0.843) and even more so for the normalized scores (κ = 0.775-0.940). Intraobserver agreement kappa values ranged from 0.753 to 0.937 for the original scores and 0.851 to 1.000 for the normalized scores. Highly significant correlations were found among the various original scores (r = 0.42-0.86, p values between 0.0296 and < 0.0001), except for VDR versus S-MRI and Terk. Normalization generally induced marginal reductions in statistical significance, whereas S-MRI versus VDR reached statistical significance with the normalized scores. CONCLUSION. Our data indicate no significant loss of statistical information is caused by the normalization we employed. Our approach therefore facilitates comparison of different scores obtained in different institutions with different imaging modalities.

To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (∆PCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response.Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ∆PCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria.Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p 0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14 s; p = 0.722). Differently, a significant reduction of all PCTp (p 0.001) including MTT (from 6.18 to 2.24 s; p = 0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p = 0.037) with the trend also at 3 weeks (p = 0.099) at the multivariate analysis.Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response.This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT.

In this issue of The Journal of Nuclear Medicine, Antoniou et al. describe a novel scintigraphic procedure designed to evaluate in a physiologic manner the transit of both the liquid and the solid components of a meal through virtually the entire gastrointestinal tract, starting with esophageal

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with (18)F-choline PET/CT in a large cohort of patients.Data from 1,000 patients who had undergone (18)F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ(2) test. Univariable and multivariable analyses were performed by logistic regression.The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1-2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of (18)F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of (18)F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1-2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive (18)F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both,0.001).A high GS at diagnosis is a strong predictive factor for positive (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Lymphoscintigraphy is an essential component for radio-guided sentinel lymph node biopsy (SLNB), which is now routinely employed in clinical practice for treating patients with breast cancer [1] or melanoma [2]. SLNB is used to assess the tumoral involvement of lymph nodes not only for staging (parameter N of the TNM [tumor, node, metastases] system) and prognostic stratification, but also for therapeutic purposes [3]. This procedure is part of the so-called “radioguided surgery,” a whole spectrum of nuclear medicine applications based on the combination of preoperative imaging, intraoperative detection, and postoperative techniques, involving close collaboration between at least three different specialties (nuclear medicine, surgery, pathology, and sometimes radiology and health physics as well) [4].