mCRPC progression of disease after [177Lu]Lu-PSMA-617 detected on [18F]Choline: a case of PCa heterogeneity.

Radioligand therapy with [177Lu]Lu-PSMA is a theranostic approach for heavily treated mCRPC patients with positive PSMA PET in the absence of relevant PSMA-negative metastases assessed through CT, MRI, bone scan or FDG PET. In this case, we described a mCRPC patient treated with RLT with discordant PSA values and PSMA images, in which Choline PET confirmed a biochemically suspected disease progression (PD), showing metastatic lesions not revealed by PSMA imaging.

PSMA-positive prostatic volume prediction with deep learning based on T2-weighted MRI.

PURPOSE: High PSMA expression might be correlated with structural characteristics such as growth patterns on histopathology, not recognized by the human eye on MRI images. Deep structural image analysis might be able to detect such differences and therefore predict if a lesion would be PSMA positive. Therefore, we aimed to train a neural network based on PSMA PET/MRI scans to predict increased prostatic PSMA uptake based on the axial T2-weighted sequence alone. MATERIAL AND METHODS: All patients undergoing simultaneous PSMA PET/MRI for PCa staging or biopsy guidance between April 2016 and December 2020 at our institution were selected. To increase the specificity of our model, the prostatic beds on PSMA PET scans were dichotomized in positive and negative regions using an SUV threshold greater than 4 to generate a PSMA PET map. Then, a C-ENet was trained on the T2 images of the training cohort to generate a predictive prostatic PSMA PET map. RESULTS: One hundred and fifty-four PSMA PET/MRI scans were available (133 [68Ga]Ga-PSMA-11 and 21 [18F]PSMA-1007). Significant cancer was present in 127 of them. The whole dataset was divided into a training cohort (n = 124) and a test cohort (n = 30). The C-ENet was able to predict the PSMA PET map with a dice similarity coefficient of 69.5 ± 15.6%. CONCLUSION: Increased prostatic PSMA uptake on PET might be estimated based on T2 MRI alone. Further investigation with larger cohorts and external validation is needed to assess whether PSMA uptake can be predicted accurately enough to help in the interpretation of mpMRI.

Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Updating 90Y Voxel S-Values including internal Bremsstrahlung: Monte Carlo study and development of an analytical model.

PURPOSE: Internal Bremsstrahlung (IB) is a process accompanying ß-decay but neglected in Voxel S-Values (VSVs) calculation. Aims of this work were to calculate, through Monte Carlo (MC) simulation, updated 90Y-VSVs including IB, and to develop an analytical model to evaluate 90Y-VSVs for any voxel size of practical interest. METHODS: GATE (Geant4 Application for Tomographic Emission) was employed for simulating voxelized geometries of soft tissue, with voxels sides l ranging from 2 to 6 mm, in steps of 0.5 mm. The central voxel was set as a homogeneous source of 90Y when IB photons are not modelled. For each l, the VSVs were computed for 90Y decays alone and for 90Y + IB. The analytical model was then built through fitting procedures of the VSVs including IB contribution. RESULTS: Comparing GATE-VSVs with and without IB, differences between + 25% and + 30% were found for distances from the central voxel larger than the maximum ß-range. The analytical model showed an agreement with MC simulations within ± 5% in the central voxel and in the Bremsstrahlung tails, for any l value examined, and relative differences lower than ± 40%, for other distances from the source. CONCLUSIONS: The presented 90Y-VSVs include for the first time the contribution due to IB, thus providing a more accurate set of dosimetric factors for three-dimensional internal dosimetry of 90Y-labelled radiopharmaceuticals and medical devices. Furthermore, the analytical model constitutes an easy and fast alternative approach for 90Y-VSVs estimation for non-standard voxel dimensions.

Thyroglobulin Value Predict Iodine-123 Imaging Result in Differentiated Thyroid Cancer Patients.

Background: In differentiated thyroid cancer (DTC) patients, the response to initial treatments is evaluated 6-12 months after radioiodine therapy (RIT) according to the 2015 American Thyroid Association (2015 ATA) criteria. In selected patients, diagnostic 131-radioiodine whole-body scintigraphy (Dx-WBS) is recommended. We evaluated the diagnostic performance of 123I-Dx-WBS-SPECT/CT imaging in detecting incomplete structural responses in the early follow-up of DTC patients and, additionally, derived optimized basal-Tg value as a yardstick for scintigraphic imaging. Methods: We reviewed the records of 124 low or intermediate-risk DTC patients with negative anti-thyroglobulin antibody. All patients had undergone (near)-total-thyroidectomy followed by RIT. The response to initial treatments was evaluated 6-12 months after RIT. Results: According to the 2015 ATA criteria, 87, 19 and 18 DTC patients were classified to have excellent response (ER), indeterminate/incomplete biochemical response (BIndR/BIR) or structural incomplete response (SIR), respectively. Among patients with less than ER, 18 had a positive 123I-Dx-WBS-SPECT/CT. Metastatic disease at 123I-Dx-WBS-SPECT/CT mainly involved lymph nodes within the central compartment, and corresponding neck ultrasound examinations were negative. The ROC curve analysis was performed to define the best basal-Tg cut-off (i.e., 0.39 ng/mL; AUC = 0.852) able to discriminate patients with and without positive 123I-Dx-WBS-SPECT/CT, respectively. The overall sensitivity, specificity, accuracy, PPV and NPV were 77.8%, 89.6%, 87.9%, 56.0% and 95.9%, respectively. Basal-Tg cut-off was an independent risk factor for having a positive 123I-Dx-WBS-SPECT/CT. Conclusion:123I-Dx-WBS-SPECT/CT identified lymph node metastases in 14/37 patients with less than ER and a negative neck ultrasound, thus modifying the management of such patients. The diagnostic performance of 123I-Dx-WBS-SPECT/CT significantly increased in patients with basal-Tg values ≥ 0.39 ng/mL.

Comparison of 1.1 GBq and 2.2 GBq Activities in Patients with Low-Risk Differentiated Thyroid Cancer Requiring Postoperative 131I Administration: A Real Life Study.

OBJECTIVES: To compare the efficacy of low and moderate 131I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. METHODS: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by 131I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8-12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. RESULTS: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate 131I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low 131I activities and three (1.8%) patients treated with moderate 131I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate 131I activities, respectively (p = 0.654). CONCLUSIONS: When 131I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease.

Internal Bremsstrahlung, the missing process in beta decay Monte Carlo simulation: The relevance in 32P Dose-Point-Kernel estimation.

PURPOSE: In nuclear medicine, Dose Point Kernels (DPKs), representing the energy deposited all around a point isotropic source, are extensively used for dosimetry and are usually obtained by Monte Carlo (MC) simulations. For beta-decaying nuclides, DPK is usually estimated neglecting Internal Bremsstrahlung (IB) emission, a process always accompanying the beta decay and consisting in the emission of photons having a continuous spectral distribution. This work aims to study the significance of IB emission for DPK estimation in the case of 32P and provide DPK values corrected for the IB photon contribution. METHODS: DPK, in terms of the scaled absorbed dose fraction, F(R/X90), was first estimated by GAMOS MC simulation using the standard beta decay spectrum of 32P, Fß(R/X90). Subsequently, an additional source term accounting for IB photons and their spectral distribution was defined and used for a further MC simulation, thus evaluating the contribution of IB emission to DPK values, Fß+IB(R/X90). The relative percent difference, δ, between the DPKs obtained by the two approaches, Fß+IB vs. Fß, was studied as a function of the radial distance, R. RESULTS: As far as the energy deposition is mainly due to the beta particles, IB photons does not significantly contribute to DPK; conversely, for larger R, Fß+IB values are higher by 30-40% than Fß. CONCLUSIONS: The inclusion of IB emission in the MC simulations for DPK estimations is recommended, as well as the use of the DPK values corrected for IB photons, here provided.

Preliminary Findings of the Role of FAPi in Prostate Cancer Theranostics.

Prostate cancer (PCa) is the most frequently diagnosed cancer worldwide and the second most common cause of cancer-related deaths among men. Progress in molecular imaging has magnified its clinical management; however, an unmet clinical need involves the identification of new imaging biomarkers that complement the gold standard of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in cases of clinically significant PCa that do not express PSMA. Fibroblast activation protein (FAP) is a type II transmembrane serine overexpressed in many solid cancers that can be imaged through quinoline-based PET tracers derived from an FAP inhibitor (FAPi). Preliminary results of FAPi application in PCa (in PSMA-negative lesions, and in comparison with fluorodeoxyglucose-FDG) are now available in the literature. FAP-targeting ligands for PCa are not limited to detection, but could also include therapeutic applications. In this preliminary review, we provide an overview of the clinical applications of FAPi ligands in PCa, summarising the main results and highlighting contemporary strengths and limitations.

Artificial Intelligence in Breast Cancer: A Systematic Review on PET Imaging Clinical Applications.

BACKGROUND: 18F-FDG PET/CT imaging represents the most important functional imaging method in oncology. European Society of Medical Oncology and the National Comprehensive Cancer Network guidelines defined a crucial role of 18F-FDG PET/CT imaging for local/locally advanced breast cancer. The application of artificial intelligence on PET images might potentially contributes in the field of precision medicine. OBJECTIVE: This review aims to summarize the clinical indications and limitations of PET imaging for comprehensive artificial intelligence in relation to breast cancer subtype, hormone receptor status, proliferation rate, and lymphonodal (LN)/distant metastatic spread, based on recent literature. METHODS: A literature search of the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases was carried out, searching for articles on the use of artificial intelligence and PET in breast tumors. The search was updated from January 2010 to October 2021 and was limited to original articles published in English and about humans. A combination of the search terms "artificial intelligence", "breast cancer", "breast tumor", "PET", "Positron emission tomography", "PET/CT", "PET/MRI", "radiomic"," texture analysis", "machine learning", "deep learning" was used. RESULTS: Twenty-three articles were selected following the PRISMA criteria from 139 records obtained from the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases according to our research strategy. The QUADAS of 30 full-text articles assessed reported seven articles that were excluded for not being relevant to population and outcomes and/or for lower level of evidence. The majority of papers were at low risk of bias and applicability. The articles were divided per topic, such as the value of PET in the staging and re-staging of breast cancer patients, including new radiopharmaceuticals and simultaneous PET/MRI. CONCLUSION: Despite the current role of AI in this field remains still undefined, several applications for PET/CT imaging are under development, with some preliminary interesting results particularly focused on the staging phase that might be clinically translated after further validation studies.

A Prospective Observational Study on the Structuring Process and Implementation of a Large Regional, Inter-hospital, Virtual Multidisciplinary Tumor Board on Prostate Cancer.

BACKGROUND/AIM: At present, multidisciplinary tumor boards (MDTB) are considered best practice in oncology. However, web-based virtualization of MDTB may increase participation in meetings, the number of cases discussed, and adherence to guidelines, deliver better treatment, and eventually improve outcomes for patients with prostate cancer. PATIENTS AND METHODS: This is an observational study focused on exploring the structuring process and implementing a multi-institutional virtual MDTB in Sicily, Italy. Other endpoints included the analysis of cooperation between participants, adherence to guidelines, patient outcomes, and patient satisfaction. RESULTS: Overall, 126 patients were referred to the virtual MDTB for a total of 302 cases discussed in an 18-month period. Nearly 45% of cases were referred from general hospitals or tertiary centers, 38% from comprehensive cancer centers, and only 17% from academic ones. Most health professional participants (95%) reported eliminating geographical barriers and consequently reducing costs and saving time as key advantages of virtual meetings over face-to-face ones. Using a specifically designed platform for virtual MDTBs was another excellent point, especially to geolocate clinical trials and time-lapse data storage. The majority of referred patients had stage T 3-4 prostate cancer (79%). Overall, 71% of proposals discussed were approved unchanged, while 19% changed after the virtual MDTB discussion. Debated points were mostly radiologic, surgical, medical, or radiation treatment-related issues. In particular, the prescriptive appropriateness of positron emission tomography with 68Ga-prostatic specific membrane antigen, newer drugs, radiation versus surgical approach, stage T3-4 cases, and adjuvant therapy represented the most debated issues. The proposed diagnostic and/or therapeutic options were controlled for adherence to the guidelines and/or updated scientific evidence. Overall, 98% of approved proposals and changes were in line with the guidelines. Overall, most participants felt virtual MDTB was very useful and case discussions led to a major change of strategy in 19% of cases. CONCLUSION: Virtual MDTBs are a very useful way to achieve best management of prostate cancer while saving time and fostering cooperation.

Peptide Receptor Radionuclide Therapy in Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma is a rare, aggressive skin malignancy, also known as neuroendocrine carcinoma of the skin, with high rates of recurrence and distant metastasis. In refractory metastatic Merkel cell carcinoma (mMCC), besides immunotherapy, chemotherapy, and radiation, peptide receptor radionuclide therapy (PRRT) may be a viable option since this type of tumor can express somatostatin receptors. Methods: We performed a comprehensive review of the literature to evaluate the efficacy of PRRT in mMCC patients. Results: Thirty-seven patients with mMCC received PRRT (1-5 cycles) with 177Lu- or 90Y-labeled somatostatin analogs (cumulative activity, 1.5-30 GBq). Radiographic response was available for 19 of 28 patients who received PRRT alone. Six (31.6%) of 19 patients showed objective responses, from partial to complete, and no severe adverse events were reported. Conclusion: Our analysis supports the use of PRRT in mMCC with sufficient somatostatin receptor uptake, although the quality of the available evidence is low. Prospective clinical trials are already in development and have started accruing in some parts of the world.

Constrictive Pericarditis: An Update on Noninvasive Multimodal Diagnosis.

Constrictive pericarditis (CP) is a rare condition that can affect the pericardium after every pericardial disease process and has been described even after SARS-CoV-2 infection or vaccine. In CP, the affected pericardium, usually the inner layer, is noncompliant, constraining the heart to a fixed maximum volume and impairing the diastolic function. This leads to several clinical features, that, however, can be pleomorphic. In its difficult diagnostic workup, noninvasive multimodal imaging plays a central role, providing important morphological and functional data, like the enhanced ventricular interdependence and the dissociation between intrathoracic and intracardiac pressures. An early and proper diagnosis is crucial to set an appropriate therapy, changing the prognosis of patients affected by CP. In this review, we cover in detail the main elements of each imaging technique, after a reminder of pathophysiology useful for understanding the diagnostic findings.

Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers.

BACKGROUND: We aimed to evaluate the role of circulating miRNAs as a biomarker of the persistence of papillary thyroid cancer (PTC) in patients with an "uninformative" thyroglobulin (Tg) measurement. METHODS: We prospectively enrolled 49 consecutive PTC patients with Tg-positive antibodies (TgAb) who had undergone a (near)-total thyroidectomy and 131I therapy (RIT). The serum thyroid stimulating hormone (TSH), Tg, and TgAb levels were measured before and at 6 and 12 months after RIT, respectively. The serum miRNA (221, 222, 375, 155, and 146b) levels were measured simultaneously. RESULTS: The response to the initial therapy was assessed according to the 2015 ATA criteria. A decrease in 50% or more of serum miRNA over time was observed in 41/49 PTC patients, who showed an excellent response (ER), but six and two patients were classified to have an indeterminate/incomplete biochemical or incomplete structural response to initial therapy. CONCLUSION: Serum miRNA kinetics emerge as a promising biomarker for the early detection of a persistent disease in PTC patients with uninformative Tg results.

An analytic model to calculate voxel s-values for177Lu.

Objective.177Lu is one of the most employed isotopes in targeted radionuclide therapies and theranostics, and 3D internal dosimetry for such procedures has great importance. Voxel S-Values (VSVs) approach is widely used for this purpose, but VSVs are available for a limited number of voxel dimensions. The aim of this work is to develop an analytic model for the calculation of177Lu-VSVs in any cubic voxelized geometry of practical interest.Approach. Monte Carlo (MC) simulations were implemented with the toolkit GAMOS to evaluate VSVs in voxelized geometries of soft tissue from a source of177Lu homogeneously distributed in the central voxel. Nine geometric setups, containing 15 × 15 × 15 cubic voxels of sideslranging from 2 mm to 6 mm, in steps of 0.5 mm, were considered. For eachl, the VSVs computed as a function of the 'normalized radius',Rn= R/l(withR = distance from the center of the source voxel), were fitted with a parametric function. The dependencies of the parameters as a function oflwere then fitted with appropriate functions, in order to implement the model for deducing177Lu-VSVs for anylwithin the aforementioned range.Main results. The MC-derived VSVs were satisfactorily compared with literature data for validation, and the VSVs computed with the analytic model agree with the MC ones within 2% forRn≤ 2 and within 6% forRn> 2.Significance. The proposed model enables the easy and fast calculation, with a simple spreadsheet, of177Lu-VSVs in any cubic voxelized geometry of practical interest, avoiding the necessity of implementingad-hocMC simulations to estimate VSVs for specific voxel dimensions not available in literature data.

Prostate Cancer Biochemical Recurrence Resulted Negative on [68Ga]Ga-PSMA-11 but Positive on [18F]Fluoromethylcholine PET/CT.

For prostate cancer (PCa) biochemical recurrence (BCR), the primarily suggested imaging technique by the European Association of Urology (EAU) guidelines is prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT). Indeed, the increased detection rate of PSMA PET/CT for early BCR has led to a fast and wide acceptance of this novel technology. However, PCa is a very heterogeneous disease, not always easily assessable with the highly specific PSMA PET with around 10% of cases occuring without PSMA expression. In this paper, we present the case of a patient with PCa BCR that resulted negative on [68Ga]Ga-PSMA-11 PET/CT, but positive on [18F]Fluoromethylcholine (Choline) PET/CT.

Gastroparesis in Adolescent Patient with Type 1 Diabetes: Severe Presentation of a Rare Pediatric Complication.

Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is clinically characterized by delayed gastric emptying and upper gastrointestinal symptoms including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for the diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric age are very scarce. We hereby report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with advanced hybrid closed loop system was successfully practiced. Pediatricians should seriously consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes.

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics.

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer.

The Utility of Conventional Amino Acid PET Radiotracers in the Evaluation of Glioma Recurrence also in Comparison with MRI.

AIM: In this comprehensive review we present an update on the most relevant studies evaluating the utility of amino acid PET radiotracers for the evaluation of glioma recurrence as compared to magnetic resonance imaging (MRI). METHODS: A literature search extended until June 2020 on the PubMed/MEDLINE literature database was conducted using the terms "high-grade glioma", "glioblastoma", "brain tumors", "positron emission tomography", "PET", "amino acid PET", "[11C]methyl-l-methionine", "[18F]fluoroethyl-tyrosine", "[18F]fluoro-l-dihydroxy-phenylalanine", "MET", "FET", "DOPA", "magnetic resonance imaging", "MRI", "advanced MRI", "magnetic resonance spectroscopy", "perfusion-weighted imaging", "diffusion-weighted imaging", "MRS", "PWI", "DWI", "hybrid PET/MR", "glioma recurrence", "pseudoprogression", "PSP", "treatment-related change", and "radiation necrosis" alone and in combination. Only original articles edited in English and about humans with at least 10 patients were included. RESULTS: Forty-four articles were finally selected. Conventional amino acid PET tracers were demonstrated to be reliable diagnostic techniques in differentiating tumor recurrence thanks to their high uptake from tumor tissue and low background in normal grey matter, giving additional and early information to standard modalities. Among them, MET-PET seems to present the highest diagnostic value but its use is limited to on-site cyclotron facilities. [18F]labelled amino acids, such as FDOPA and FET, were developed to provide a more suitable PET tracer for routine clinical applications, and demonstrated similar diagnostic performance. When compared to the gold standard MRI, amino acid PET provides complementary and comparable information to standard modalities and seems to represent an essential tool in the differentiation between tumor recurrence and other entities such as pseudoprogression, radiation necrosis, and pseudoresponse. CONCLUSIONS: Despite the introduction of new advanced imaging techniques, the diagnosis of glioma recurrence remains challenging. In this scenario, the growing knowledge about imaging techniques and analysis, such as the combined PET/MRI and the application of artificial intelligence (AI) and machine learning (ML), could represent promising tools to face this difficult and debated clinical issue.

Radiomics Analysis of Brain [18F]FDG PET/CT to Predict Alzheimer's Disease in Patients with Amyloid PET Positivity: A Preliminary Report on the Application of SPM Cortical Segmentation, Pyradiomics and Machine-Learning Analysis.

BACKGROUND: Early in-vivo diagnosis of Alzheimer's disease (AD) is crucial for accurate management of patients, in particular, to select subjects with mild cognitive impairment (MCI) that may evolve into AD, and to define other types of MCI non-AD patients. The application of artificial intelligence to functional brain [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography(CT) aiming to increase diagnostic accuracy in the diagnosis of AD is still undetermined. In this field, we propose a radiomics analysis on advanced imaging segmentation method Statistical Parametric Mapping (SPM)-based completed with a Machine-Learning (ML) application to predict the diagnosis of AD, also by comparing the results with following Amyloid-PET and final clinical diagnosis. METHODS: From July 2016 to September 2017, 43 patients underwent PET/CT scans with FDG and Florbetaben brain PET/CT and at least 24 months of clinical/instrumental follow-up. Patients were retrospectively evaluated by a multidisciplinary team (MDT = Neurologist, Psychologist, Radiologist, Nuclear Medicine Physician, Laboratory Clinic) at the G. Giglio Institute in Cefalù, Italy. Starting from the cerebral segmentations applied by SPM on the main cortical macro-areas of each patient, Pyradiomics was used for the feature extraction process; subsequently, an innovative descriptive-inferential mixed sequential approach and a machine learning algorithm (i.e., discriminant analysis) were used to obtain the best diagnostic performance in prediction of amyloid deposition and the final diagnosis of AD. RESULTS: A total of 11 radiomics features significantly predictive of cortical beta-amyloid deposition (n = 6) and AD (n = 5) were found. Among them, two higher-order features (original_glcm_Idmn and original_glcm_Id), extracted from the limbic enthorinal cortical area (ROI-1) in the FDG-PET/CT images, predicted the positivity of Amyloid-PET/CT scans with maximum values of sensitivity (SS), specificity (SP), precision (PR) and accuracy (AC) of 84.92%, 75.13%, 73.75%, and 79.56%, respectively. Conversely, for the prediction of the clinical-instrumental final diagnosis of AD, the best performance was obtained by two higher-order features (original_glcm_MCC and original_glcm_Maximum Probability) extracted from ROI-2 (frontal cortex) with a SS, SP, PR and AC of 75.16%, 80.50%, 77.68%, and 78.05%, respectively, and by one higher-order feature (original_glcm_Idmn) extracted from ROI-3 (medial Temporal cortex; SS = 80.88%, SP = 76.85%, PR = 75.63%, AC = 78.76%. CONCLUSIONS: The results obtained in this preliminary study support advanced segmentation of cortical areas typically involved in early AD on FDG PET/CT brain images, and radiomics analysis for the identification of specific high-order features to predict Amyloid deposition and final diagnosis of AD.