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Unruptured brain arteriovenous malformations (AVM) have a heterogeneous clinical presentation, mainly related to the presence of intracerebral hemorrhage. We report the diagnosis of AVM in a patient with Parkinson's disease (PD), who undergone positron emission tomography/magnetic resonance imaging (PET/MRI) molecular brain imaging with fluorine-18-dihydroxyphenylalanine (F-18-DOPA). This case suggests that AVM may be occasionally recognized in molecular imaging studies using positron-emitting amino acids. Magnetic resonance imaging with susceptibility-weighted imaging (SWI) sequences and 3D time of flight (TOF) reconstruction may contribute to manage patients with AVM.

Nuclear medicine in NENs covers a pivotal role, both in diagnostics and in therapy, outlining the concept of theragnostic approach, bases on radiopharmaceuticals. The whole theme is based on the overexpression of somatostatin receptors (SSTRs), membrane molecule that allow the feasibility of this techniques, mediating the interaction between the drug and the targeted neoplastic cells, in order to depict it or to kill it, depending on the radiopharmaceutical’s purpose: this molecular background will be the main focus of this paper, from native somatostatin and receptors to the concept of internalization. Today, the gold standard in nuclear medicine in this context is represented by 68GaDOTA-peptides in association with PET/CT, but other important techniques and radiotracers will also be presented. Finally, some clinical condition, in which these techniques are employed, will be presented, such as GEP-NETs, lung NETs, unknown primary NETs (CUP lesions) and metastases.

Theragnostics is not a new conception, even if nowadays it is gaining more and more importance in clinical practice and interest among researchers, thanks to their great results obtained in oncologic (especially in neuroendocrine tumors) and non-oncologic fields, too. A theragnostic approach is synthesizable in “see what you treat and treat what you see”, in other words a strategy that has the goal to be in between diagnostics and therapy. Theragnostics is founded on functional and biological characteristics of diseases, on which is based radiopharmaceuticals’ development, there is to say very specific drugs able to bind a precise target and labeled to a particular radionuclide, that is specifically chosen depending on its diagnostic or therapeutic purpose. In this paper, the Authors will focus the attention on several current and promising future application of theragnostics in several clinical scenarios, starting from neuroendocrine tumors (one of the most active sectors in this field), differentiated thyroid carcinoma, neuroblastoma and pheochromocytoma/paraganglioma, castration-resistant prostatic cancer, liver neoplastic lesions (metastases and/or hepatocellular carcinoma) through SIRT/TARE locoregional techniques.

Prostate cancer (PCa) provides different types of approach, both as regards the diagnostic and therapeutic aspects, based on the stage of disease. Nowadays, multi-parametric MRI (mpMRI) plays a pivotal role in primary prostate cancer diagnosis and opens the door to the planning of therapeutic st In this fields, conventional morphological imaging showed limited accuracy for assessment of biochemical recurrent prostate cancer (BRPCa), advanced disease and post-therapy monitoring and evaluations. Nuclear medicine has a metabolic or receptor point of view that is often helpful in situations where morphological analysis is not enough. Radiolabeled choline (11C or 18F), base its use on the exalted neoplastic cell membranes turnover and phosphatidylcholine production increase. Thanks to its features, 68Ga-PSMA PET imaging is affirming in entire PCa diagnostic scenario: from local recurrence and advanced disease to primary tumor localization and lymph nodes disease detection; up to the most future-oriented applications that include radio guided surgery (RGS) and theranostics with 177Lu-PSMA. Having achieved excellent levels of diagnostic accuracy does not stop nuclear medicine research which for these comparison scenarios today also proposes the use of 11C-acetate and 18-Fluciclovine that undermine choline PET/CT and PSMA PET/CT results, in a race for the best possible diagnostic performance. Nuclear medicine is also very active in the study of “bone scenario”, it represent an essential evaluation for correct defining the disease stage. As for diagnostics, also in the therapy’s field we observe the flowering of new solutions, to try to improve both the survival and the quality of life of the patient: 223Ra-dichloride and 177Lu-PSMA are two of the most brilliant examples. Finally, the look towards the future cannot ignore the advent of hybrid systems; from this point of view the diamond shining in the near future undoubtedly seems to be PET/MRI, fixing the maximum anatomical definition with finest metabolic-receptor informations.

Prostate Cancer (PCa) represents the most common malignant tumor in men but according to the European Association of Urology (EAU) guidelines, a mass screening for PCa diagnosis should not be performed due to over-diagnosis and over-treatment related problems. An early clinical diagnosis is possible, mainly based on digital rectal examination and Prostatic Specific Agent (PSA) testing. However, the only mandatory test to define the presence of PCa is ultrasound guided-biopsy, obtained on multiple samples, which has also a high prognostic value. In this context, diagnostic imaging plays an important role as confirmed by EAU that in a 2016 update of their guidelines on PCa stated the importance of Positron Emission Tomography (PET) with11C- or18F-choline combined with computed tomography (CT) to identify local relapse, lymph node involvement and metastatic spread at all stages. Consequently, in 2017, the European Association of Nuclear Medicine (EANM) together with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published new guidelines for68Ga-Prostate Specific Membrane Antigen (PSMA) PET/CT to help physicians in the recommendation, execution and interpretation of PET/CT scans in patients with PCa. Thus, the aim of this 'evidence paper' is to define the current diagnostic algorithm in PCa in order to increase the general level of confidence in approaching such a crucial topic.

Choline is a quaternary ammonium base that represents an essential component of phospholipids and cell membranes. Malignant transformation is associated with an abnormal choline metabolism at a higher levels with respect to those exclusively due to cell multiplication. The use of Positron Emission Tomography/Computed Tomography (PET/CT) with radiocholine (RCH), labeled with 11 C or 18 F, is widely diffuse in oncology, with main reference to restaging of patients with prostate cancer. In this paper we have analyzed the most important issues related to the possible utilization of RCH in diagnostic imaging of human cancer.

Technical advances in computed tomography (CT), including helical CT and multidetector CT, have resulted in an improved ability to evaluate the small intestine. CT examination of the small bowel requires the use of dedicated techniques for optimal evaluation of inflammatory bowel disease in order to select the most appropriate therapeutic strategy for the individual patient and to monitor disease progression over time.Although intraluminal contrast media combined with intravenous iodinated contrast agents with a biphasic injection protocol provide good visualization of the typical lesions of the disease, accurate estimation of the degree of disease activity can only be achieved with nuclear imaging. Owing to continuous technical improvements, magnetic resonance imaging is expected to play an increasing role in the near future. However, in selected patients, three-dimensional endoanal ultrasonography remains the gold standard technique for assessing the anal sphincter and the recto-anal junction.

Anatomopathological classification of Neuroendocrine tumors (NETs), today, covers a pivotal role in correctly identifying the disease and establish the right diagnostic and therapeutic approach it is needed in order to manage the patient. Depending on its grading and staging, NENs can have very different prognostic perspectives. Basing on WHO 2017 classification, in this paper will be explored their main characteristics, diving into main histotypes, dividing them into functional and non-functional tumors, keeping in mind their main locations: gastroenteropancreatic tract and lungs. Their typical clinical presentation and diagnostic strategies will be explained, mainly focusing on nuclear medicine and the importance of receptor overexpression (especially represented by somatostatin receptors, or SSTRs). This is the knowledge on which is based the diagnostic and therapeutic approach with peptide radiopharmaceuticals, especially 68Ga-DOTA-peptides (today, the gold standard in well-differentiated neuroendocrine neoplasms, only with the exception of insulinoma, that shows a low density of these molecules on its cellular surface).

Diagnostics and therapy in neuroendocrine tumors (NETs) has been heavily influenced by nuclear medicine progresses, both from a diagnostic and therapeutic perspective. The introduction of somatostatin-based peptides, labeled to radionuclides (constituting radiopharmaceuticals), such as the current golden standard 68Ga-DOTA-SSAs (SomatoStatin Analogues), has revolutionized the approach to these neoplasms. Peptides-based drugs in NENs’ management have been introduced with OctreoScan® (111In-DTPA-octreotide) in combination with scintigraphy, but today techniques have deeply evolved, allowing better performance together with higher accuracy and sensitivity, in addition to image quality improvements (also in terms of details and anatomical data), especially thanks to the implementation of hybrid techniques, such as SPECT/CT and PET/CT. 68Ga-based radiotracers are not the only diagnostic option in NENs, because of the existence of several tumors (such as insulinomas or malignant neoplasms) that do not express SSAs’ target molecules, thus the utilization of other radiocompunds is needed, such as 18F-FDG.

Prostate cancer (PCa) is considered a major challenge for the many medical disciplines that deal with it; despite the diagnostic and therapeutic improvement, it remains for male sex the most common neoplasm and one of the major causes of death. Clinical presentation is classically varied and can change in relation to the disease state. The diagnostic suspicion must trigger some evaluations by a team of specialists: both biochemical and clinical. To date, despite the galaxy of new diagnostic technologies available, the first steps are still being conducted on the track that sees a central role of serum PSA levels and digito-rectal exploration (DRE). Currently an increasingly emerging role in this field is occupied by MRI, so much so that we can speak of an MRI-targeted biopsy (MRI-TB); in fact, through various methods of use, we try to improve the quality of the samples in order to have more and more accurate biopsies focused on the disease areas. The possibility of using increasingly specific sequences such as diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE) and MR spectctroscopy (MRS) certainly places it at the center of the diagnostic step of this phase of disease. Also from a therapeutic point of view there have been great steps forward in recent years, for both non-metastatic and metastatic disease. In both the diagnostic and therapeutic fields, alongside conventional radiological and pharmacological techniques, nuclear medicine is in a very useful position. In an increasingly targeted approach and in an increasingly “precise” medicine, radiopharmaceuticals such as Ra-223 dichloride and 177Lu-PSMA represent the new frontiers of prostate cancer treatment.

Diagnostics and therapy in neuroendocrine tumors (NETs) has been heavily influenced by nuclear medicine progresses, both from a diagnostic and therapeutic perspective. The introduction of somatostatin-based peptides, labeled to radionuclides (constituting radiopharmaceuticals), such as the current golden standard 68Ga-DOTA-SSAs (SomatoStatin Analogues), has revolutionized the approach to these neoplasms. That is not all: these radiopharmaceuticals have been employed also into a therapeutic context, realizing the so-called PRRT (peptide receptor radionuclide therapy), allowing NENs to be integrated into a comprehensive theragnostic approach, making advantage of the knowledge based on receptor overexpression of neuroendocrine tumors, in particular SSTRs (somatostatin receptors). PRRT is mainly focused on the utilization of 90Y-and 177Lu-based peptides, but in this case another important factor is needed: the internalization process, a pivotal phenomenon that allows the efficacy of the therapy, thanks to the intracellular collection of radioisotopes: in this way, they are able to damage internal structures of neoplastic cells.

After esophagectomy, the stomach is usually used to restore digestive continuity. To prevent postoperative delayed gastric emptying, most authors perform a gastric drainage procedure or transpose a tubulized stomach. The aim of our work is to evaluate the emptying of a transposed whole stomach without performing a pyloromyotomy or a pyloroplasty. From 1996 to January 2004, 45 patients underwent total esophagectomy for cancer or for caustic stenosis. Reconstruction of digestive continuity was realized through transposition of the whole stomach without performing a pyloric drainage procedure. At 12 months after the intervention, 35 patients (77.8%; 20 men and 15 women), with a mean age of 63.4 years, were submitted to a gastric emptying scintigraphic study by means of ingestion of a mixed meal labeled with 37 MBq 99mTc-sulfur colloid. Imaging of the gastric contents was acquired immediately before and after for 240 minutes at 10-minute intervals. The half-emptying time was defined as the time to emptying of 50% of the gastric content measured at time 0. A control group included 20 patients who underwent total esophagectomy with transposition of a tubulized stomach and cervical anastomosis. Mean half-emptying time was 71.4 minutes (range, 15–90 minutes; control group, 68.7 minutes; reference range, 83 * 34 minutes): all the patients were in the normal range except one with a half-emptying time of 15 minutes. No patient presented a gastric retention of >10% of the gastric meal at 4 hours. No patient complained of delayed gastric emptying symptoms. After esophagectomy, the transposition of the whole stomach without a pyloric drainage procedure seems to be an interesting option, simplifying the surgical procedure, and is not associated with delayed gastric emptying. After esophagectomy, the stomach is usually used to restore digestive continuity. To prevent postoperative delayed gastric emptying, most authors perform a gastric drainage procedure or transpose a tubulized stomach. The aim of our work is to evaluate the emptying of a transposed whole stomach without performing a pyloromyotomy or a pyloroplasty. From 1996 to January 2004, 45 patients underwent total esophagectomy for cancer or for caustic stenosis. Reconstruction of digestive continuity was realized through transposition of the whole stomach without performing a pyloric drainage procedure. At 12 months after the intervention, 35 patients (77.8%; 20 men and 15 women) were submitted to a gastric emptying scintigraphic study by means of ingestion of a mixed meal labeled with 37 MBq 99mTc-sulfur colloid. Mean half-emptying time was 71.4 minutes (range, 15-90 minutes; reference range, 83 ± 34 minutes): all the patients were in the normal range except one. No patient complained of delayed gastric emptying symptoms. After esophagectomy, the transposition of the whole stomach without a pyloric drainage procedure seems to be an interesting option, and is not associated with delayed gastric emptying.

Today, positron emission tomography (PET) using F-18 Fluoro-deoxyglucose (FDG) is, when available, the most important nuclear medicine procedure applied to oncology. Nevertheless, 2 main reasons for the clinical use of somatostatin analogues labeled with single photon emitting radionuclides are: a) the low accuracy of PET-FDG in neuroendocrine tumors (NET); b) the expression of somatostatin receptors (sstr) in most cells deriving from so-called neuroendocrine dispersed cells. The latter forms the premise for the use of radiolabeled somatostatin analogues, and (111)In pentetreotide (Octreo-scan) in particular, in the diagnosis of NET and other pathological conditions, including some benign diseases. Alongside diagnosis, staging and follow-up of NET, somatostatin analogues, whether radiolabeled or not, can have a role in evaluating prognosis and predicting therapeutic efficacy in cancer patients. Interesting indications have emerged with radioguided surgery and in diagnosing the activity of disease in patients with Graves' disease (exophthalmos), sarcoidosis, and rheumatoid arthritis. The pathophysiological premises to imaging, starting from an analysis of cells expressing sstr, binding affinity of octreotide for sstr, in vivo uptake of Octreoscan in lesions expressing or not sstr are discussed, as is the possible role of quantitative receptor scintigraphy in improving diagnostic accuracy based on tumor expression of sstr.

Diagnostic strategy in thyroid cancer is conditioned by epidemiological, pathophysiological, cost-effective issues changing with age and countries. Nuclear medicine has a role mainly in differentiated carcinomas, i.e. in the large majority of thyroid cancers. In diagnosis of thyroid nodule 99mTc-perthecnetate is indicated in patients with low TSH levels, multinodular goiter, solid nodules at US negative at FNA. Radiolabeled somatostatin analogs or Metaiodobenzylguanidine (MIBG) can be used in suspicion of medullary carcinoma. There is no role in staging. WBS with 131I has a role after surgical resection of the thyroid gland and it is no more suggested before ablative therapy, because of the possible stunning effect. In the follow-up thyroglobulin (Tg) test is mandatory both after therapy withdrawal or after rhTSH administration. Some authors already suggest to use this test alone, as 1st step, in patients with differentiated carcinoma at low risk of recurrence, but this approach is not yet generally accepted and it has not yet been validated in tumors at intermediate/high risk. WBS with 131I is ever indicated when autoantibodies can affect reliability of Tg values and in presence of high Tg levels to better define a radiometabolic therapy. In case of negative WBS, PETFDG can be proposed. In WBS, 123I can be an alternative to 131I , but it is not yet generally accepted mainly because of its higher costs. The clinical use of rhTSH to increase accuracy both of Tg and WBS can be already accepted in patients at high risk following hypothyroidism, with a worst prognosis or a low pituitary response.

A 62 years old woman 6 months after left total hip prosthesis referred to our institution for persistent pain and warm, stiff, and swollen joint. 18F-FDG CT/PET Images showed an intense focal uptake corresponding to the external margin of inter-trochanteric region of prosthesis and inside the stem inferiorly, but common decision was to reconstruct PET images without attenuation correction and now showed a complete and unexpected disappearance of focal and pathological FDG uptake. This case shows the potential propagation of CT artifacts into PET emission data close to metal implants and should be taken in account together to SUV values.

Thyroid cancer (TC) represents less than 1% of all newly diagnosed malignancies. In some selected cases, with a high clinical suspicion for disease but negative I-131 scan, positron emission tomography/computed tomography (PET) with F-18-Fluorodeoxyglucose (FDG) could be helpful in the detection of disease and the definition of its extent. FDG PET/CT, better if performed after TSH stimulation analogously to patient preparation done for radioiodine scintigraphy, could be useful mainly in the detection of metastatic and recurrent disease since the uptake and diagnostic sensitivity of FDG are increased by TSH stimulation. Recently, the role of oncogenic mutations in the tumorigenesis of TCs has become clearer. Among such mutations, BRAFV600E represents the most common genetic alteration. Mutated BRAF may define a more aggressive papillary carcinoma with poorer prognosis and therefore its analysis has been extensively studied as a rule-in test for thyroid carcinoma. In this paper, we try to outline the possible role of FDG PET/CT in the management of patients with TC and positive BRAF mutations and the impact that it could have on their therapeutic algorithm, in terms of thyroidectomy and radioactive iodine (RAI) therapy.

Magnetic resonance imaging (MRI) offers excellent spatial and contrast resolution for evaluating a wide variety of pathologies, without exposing patients to ionizing radiations. Additionally, MRI offers reproducible diagnostic imaging results that are not operator-dependent, a major advantage over ultrasound. MRI is commonly used in pregnant women to evaluate, most frequently, acute abdominal and pelvic pain or placental abnormalities, as well as neurological or fetal abnormalities, infections, or neoplasms. However, to date, our knowledge about MRI safety during pregnancy, especially about the administration of gadolinium-based contrast agents, which are able to cross the placental barrier, is still limited, raising concerns about possible negative effects on both the mother and the health of the fetus. Contrast agents that are unable to cross the placenta in a way that is safe for the fetus are desirable. In recent years, some preclinical studies, carried out in rodent models, have evaluated the role of long circulating liposomal nanoparticle-based blood-pool gadolinium contrast agents that do not penetrate the placental barrier due to their size and therefore do not expose the fetus to the contrast agent during pregnancy, preserving it from any hypothetical risks. Hence, we performed a literature review focusing on contrast and non-contrast MRI use during pregnancy.

In our study, we added a three-dimensional automated breast ultrasound (3D ABUS) to mammography to evaluate the performance and cancer detection rate of mammography alone or with the addition of 3D prone ABUS in women with dense breasts. Our prospective observational study was based on the screening of 1165 asymptomatic women with dense breasts who selected independent of risk factors. The results evaluated include the cancers detected between June 2017 and February 2019, and all surveys were subjected to a double reading. Mammography detected four cancers, while mammography combined with a prone Sofia system (3D ABUS) doubled the detection rate, with eight instances of cancer being found. The diagnostic yield difference was 3.4 per 1000. Mammography alone was subjected to a recall rate of 14.5 for 1000 women, while mammography combined with 3D prone ABUS resulted in a recall rate of 26.6 per 1000 women. We also observed an additional 12.1 recalls per 1000 women screened. Integrating full-field digital mammography (FFDM) with 3D prone ABUS in women with high breast density increases and improves breast cancer detection rates in a significant manner, including small and invasive cancers, and it has a tolerable impact on recall rate. Moreover, 3D prone ABUS performance results are comparable with the performance results of the supine 3D ABUS system.