This mini-review provides an updated overview of SPECT-based radiomics in oncology, summarizing clinical applications, highlighting SPECT-specific technical considerations, and identifying priorities for future research. A structured search of MEDLINE and Scopus was performed using the terms “SPECT,” “radiomics,” and “oncology.” Only original clinical studies published in English within the last five years were included. Eligible articles were screened and grouped by oncologic topic. Eleven studies met the inclusion criteria. The reported applications included differentiation of metastatic versus benign bone lesions using bone SPECT/CT, prediction of survival in neuroblastoma with 123I-mIBG SPECT/CT, and characterization of indeterminate renal masses with 99mTc-sestamibi. Early work in radiodosiomics showed potential for estimating absorbed doses during peptide receptor radionuclide therapy and predicting response to selective internal radiation therapy. SPECT radiomics and radiodosiomics show promise for quantitative oncologic imaging, but the evidence base remains limited by small, retrospective, single-center studies and the complete absence of external validation. Standardizing acquisition and reconstruction protocols, and multicenter studies are essential to enable translation of SPECT-based radiomics into routine clinical practice.

To compare semiquantitative striatal indices produced by two widely used quantification platforms — BasGanV2™ and NeuroTrans3D (Oasis©) — for ¹²³I-Ioflupane DAT SPECT, to evaluate their diagnostic performance for Parkinson’s disease (PD) versus non-degenerative presentations, and to determine whether supervised machine-learning (ML) classifiers can clarify relative utility of the two methods. Retrospective analysis of 90 consecutive subjects (48 PD, 42 not-PD) undergoing routine ¹²³I-Ioflupane SPECT. Striatal binding ratios (caudate and putamen, left and right) were computed with both tools. Distributional differences were tested (Mann–Whitney U and Brown–Forsythe/Levene tests). Three supervised classifiers (Gaussian naïve Bayes, k-nearest neighbours, and SVM-RBF) were trained on four regional metrics from each tool using stratified shuffle-split (60:40 train: test) repeated 50 times; performance was summarised as mean (95

Introduction: Long-acting injectable antiretroviral therapy (ART) with Cabotegravir (CAB) and Rilpivirine (RPV) offers an alternative to daily oral regimens, improving adherence and patient satisfaction. However, its impact on body composition and metabolism remains underexplored. Methods: We conducted a prospective cohort study involving 29 people with HIV initiating CAB + RPV LA at a single centre in Italy. Body composition was assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) at baseline, 24 and 48 weeks. Anthropometrics, laboratory parameters and patient-reported outcomes were also collected. Statistical comparisons across time points were performed using paired tests (p <0.05 considered significant). Results: At 48 weeks, weight and BMI remained stable. Waist circumference significantly decreased (median 97 (IQR 91-102) to 94 (IQR 89-98) cm, p = 0.026), with no significant change in total fat percentage or visceral adipose tissue. A modest but statistically significant increase in trunk/limb fat ratio (mean 1.19 (SD 0.39) to 1.25 (SD 0.41), p = 0.035). Lean mass and muscle function were unchanged. BIA findings confirmed stable fat mass and body water compartments. Virologic suppression was maintained in all participants throughout follow-up. High-density lipoprotein (HDL) cholesterol increased significantly, accompanied by a rise in total cholesterol, while low-density lipoprotein (LDL) cholesterol, triglycerides and the total cholesterol/HDL ratio remained stable. Serum creatinine significantly decreased, mainly among individuals switching from bictegravir-or dolutegravir-based regimens. Glycaemia, insulin, HOMA-IR, Metabolic Score for Insulin Resistance (METS-IR), liver enzymes and hepatic steatosis and fibrosis indices remained stable. Adverse events, mostly injection-site reactions, decreased over time. Only one participant discontinued treatment. Treatment satisfaction improved throughout the study. Conclusion: CAB + RPV LA was not associated with significant weight gain, clinically relevant changes in body composition or adverse metabolic effects over 48 weeks. Virologic suppression was maintained, renal laboratory parameters improved in prior INSTI users and treatment was well tolerated with increasing satisfaction. These findings support CAB + RPV LA as a safe, effective and metabolically neutral alternative to daily oral ART.

To assess machine learning (ML) classifiers trained on harmonised multicentre ¹²³I-mIBG planar scintigraphy for differentiating Parkinson’s disease (PD) from non-PD parkinsonian syndromes and to determine whether early imaging alone may ensure accurate discrimination. This retrospective study included patients with suspected PD who underwent early ( 15 min) and delayed ( 240 min) imaging and received a definitive diagnosis after ≥ 12 months. Harmonised region of interest (ROI) placement and ComBat correction were applied. Early and late heart-to-mediastinum (H/M) ratios and washout rate (WR) were calculated. Differences were tested by Mann-Whitney U test, and cut-points identified by ROC analysis. Logistic regression, Gaussian naïve Bayes, and support vector machine were trained on these features with Z-score normalisation and synthetic minority oversampling technique (SMOTE). 127 patients were analysed (85 PD, 42 non-PD). Early and late H/M ratios were significantly lower in PD than non-PD (early H/M 1.45 ± 0.20 vs. 1.80 ± 0.20; late H/M 1.33 ± 0.22 vs. 1.68 ± 0.21; both p < 0.001). WR was modestly higher in PD (8.74 ± 5.76

Synaptic loss is a core pathological feature of neurodegenerative disorders and closely relates to cognitive and functional decline. Positron emission tomography (PET) targeting synaptic vesicle glycoprotein 2A (SV2A) has recently emerged as a promising tool for the indirect assessment of presynaptic alterations in the living human brain. This leading article discusses the evolving clinical landscape of SV2A PET across the neurodegenerative spectrum, emphasizing its translational trajectory and emerging applications. Current evidence spans Alzheimer's disease (AD), other dementias, movement disorders, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The literature is currently dominated by PET with [11C]UCB-J, while [18F]-labeled tracers, particularly [18F]SynVesT-1, are expanding clinical feasibility through longer half-life and broader distribution potential. Across disorders, PET consistently detected SV2A reductions that frequently correlated with cognition, disease severity, and complementary biomarkers, including amyloid, tau, glucose metabolism, and dopaminergic imaging. Although the field remains limited by small cohorts, heterogeneous quantification strategies, and incomplete longitudinal validation, SV2A PET is rapidly evolving into a promising translational tool for studying synaptopathies and monitoring disease progression.

Background/Objectives: The prognostic value of baseline clinical parameters in predicting the survival prolonging effect of Radium-223-dichloride (223RaCl2) for metastatic castration resistant prostate cancer (mCRPC) patients has been the object of intensive research and remains an open issue. This national multicenter study aimed to corroborate the evidence of ten years of clinical experience with 223RaCl2 by collecting data from eight Italian Nuclear Medicine Units. Methods: Data from 581 consecutive mCRPC patients treated with 223RaCl2 were retrospectively analyzed. Several baseline variables relevant to the overall survival (OS) analysis were considered, including age, previous radical prostatectomy/radiotherapy, number of previous treatment lines, prior chemotherapy, Gleason score, presence of lymphoadenopaties, number of bone metastases, concomitant use of bisphosphonates/Denosumab, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), as well as baseline values of hemoglobin (Hb), platelets, Total Alkaline Phosphatase (tALP), Lactate Dehydrogenase (LDH), and Prostate-Specific Antigen (PSA). Data were summarized using descriptive statistics, univariate analysis and multivariate analysis with the Cox model. Results: The median OS time was 14 months (95%CI 12-17 months). At univariate analysis age, the number of previous treatment lines, number of bone metastases, ECOG-PS, presence of lymphadenopathies at the time of enrollment, as well as baseline tALP, PSA, and Hb, were independently associated with OS. After multivariate analysis, the number of previous treatment lines (HR = 1.1670, CI = 1.0095-1.3491, p = 0.0368), the prior chemotherapy (HR = 0.6461, CI = 0.4372-0.9549, p = 0.0284), the presence of lymphadenopathies (HR = 1.5083, CI = 1.1210-2.0296, p = 0.0066), the number of bone metastases (HR = 0.6990, CI = 0.5416-0.9020, p = 0.0059), ECOG-PS (HR = 1.3551, CI = 1.1238-1.6339, p = 0.0015), and baseline values of tALP (HR = 1.0008, CI = 1.0003-1.0013, p = 0.0016) and PSA (HR = 1.0004, CI = 1.0002-1.0006, p = 0.0005) remained statistically significant. Conclusions: In the era of precision medicine and in the landscape of novel therapies for mCRPC, the prognostic stratification of patients undergoing 223RaCl2 has a fundamental role for clinical decision-making, ranging from treatment choice to optimal sequencing and potential associations. This large Italian multicenter study corroborated the prognostic value of several variables, emerging from ten years of clinical experience with 223RaCl2.

Planar cardiac scintigraphy with [123I]I-mIBG is widely used to image myocardial sympathetic activity. In multicentre studies, different γ-cameras can cause variability in quantitative parameters. This study aimed to harmonise multicentre [123I]I-mIBG data using a custom-designed phantom and to assess its feasibility and acceptability. A ‘tube and bottle’ phantom was designed to standardise the heart-to-mediastinum (H/M) ratio across 15 centres. Each centre prepared three versions of the phantom (A, B, and C) with varying pertechnetate ([99mTc]Tc-O4-) activities, acquired static images using their own γ-camera, and uploaded DICOM data to a shared platform. In the phantom, the tube and bottle represent the heart and mediastinum, respectively, with the tube-to-bottle (T/B) ratio simulating the H/M ratio. The reference centre analysed the images and calculated the T/B ratios, applying linear regression for data harmonisation. A survey was conducted to assess the phantom’s usability. The harmonised T/B ratios for versions A and B were 20.46 ± 0.78 and 6.19 ± 0.39, respectively. The average slope and intercept of the regression line across the participating centres resulted in 1.07 ± 0.38 and − 0.82 ± 4.95. Survey feedback indicated high feasibility and acceptability, with all centres recommending the phantom for multicentre harmonisation. The custom-made phantom effectively harmonised experimental data across different centres, supporting its use in multicentre studies to improve data consistency.

Background: Differentiating Parkinson’s disease (PD) from essential tremor (ET) is often challenging, especially in early or atypical cases. Dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with 123I-Ioflupane supports diagnosis, and semi-quantitative tools such as DaTQUANT® and BasGanV2™ provide objective measures. This study compared their diagnostic performance when integrated with supervised machine learning. Methods: We retrospectively analysed 123I-Ioflupane SPECT scans from 169 patients (133 PD, 36 ET). Semi-quantitative analysis was performed using DaTQUANT® v2.0 and BasGanV2™ v.2. Classification tree (ClT), k-nearest neighbour (k-NN), and support vector machine (SVM) models were trained and validated with stratified shuffle split (250 iterations). Diagnostic accuracy was compared between the two software packages. Results: All classifiers reliably distinguished PD from ET. DaTQUANT® consistently achieved higher accuracy than BasGanV2™: 93.8%, 93.2%, and 94.5% for ClT, k-NN, and SVM, respectively, versus 90.9%, 91.7%, and 91.9% for BasGanV2™ (p < 0.001). Sensitivity and specificity were also consistently higher for DaTQUANT® than BasGanV2. Class imbalance (PD > ET) was addressed using Synthetic Minority Over-sampling Technique (SMOTE). Conclusions: Machine learning analysis of 123I-Ioflupane SPECT enhances differentiation between PD and ET. DaTQUANT® outperformed BasGanV2™, suggesting greater suitability for AI-driven decision support. These findings support the integration of semi-quantitative and AI-based approaches into clinical workflows and highlight the need for harmonised methodologies in movement disorder imaging.

Background/Objectives: Recent studies reported that 18F-Fluorodeoxyglucose (FDG) positron –emission tomography/computed tomography (PET/CT), even in comparison with other traditional methods, can play a role in diagnosing AE and supporting early treatment. In the present study, we further investigated whether 18F-FDG PET/CT may be a complementary diagnostic tool to conventional procedures in patients with acute symptoms of suspected AE in the early phase. Methods: Eleven consecutive patients with recent acute symptoms suggestive of AE were retrospectively enrolled and underwent brain PET/CT after receiving an intravenous injection of 3.7 MBq/kg of 18F-FDG. Results: PET/CT showed abnormal FDG uptake in 9/11 patients classified as AE, while it was negative in the remaining 2/11 cases with vascular lesions. Magnetic resonance imaging (MRI), conducted in only 10/11 cases—one patient was a pacemaker wearer—identified suspected AE areas in 3/10 cases, ischemic lesions in another 3/10, and nonspecific data in the remaining 4/10 cases. Cerebrospinal fluid (CSF) tests revealed autoantibody delayed occurrence only in three patients (anti-GAD65, anti-Ma2, and anti-LGI1). After first-line treatment, 3/9 patients showed clinical improvement. Another 3/9 patients experienced partial improvement but with recurrence and new AE brain areas identified by PET/CT, which also detected favorable responses to second-line treatment in 2/3 cases. The remaining 3/9 patients, who were not responsive to treatment, ultimately died. Conclusions: In this study, PET/CT was effective in early identification of AE and enabling rapid therapy, even with inconclusive MRI and persistently negative or delayed positive CSF tests. PET/CT may aid in evaluating treatment response and detecting relapse. Notably, a negative PET/CT was associated with AE absence.

Nanotechnology has revolutionized the field of diagnostics and therapy in oncology, particularly for brain tumors and metastases. Radiolabelled nanoparticles, due to their ability to cross the blood-brain barrier and selectively accumulate in tumor tissues, emerge as key tools for both diagnosis and treatment. We studied their integration with SPECT and PET, which has improved imaging sensitivity and specificity. Their application in nanotheranostics opens new perspectives for more effective diagnostic and therapeutic strategies. A systematic literature review was conducted using PubMed, Scopus and Embase databases (last update November 2024), with keywords related to brain tumors, nanoparticles, radiopharmaceuticals, PET, SPECT, and therapy. Relevant studies on the application of radiolabelled nanotechnologies for both diagnosis and treatment of primary and metastatic brain tumors were selected. In diagnostics, liposomes, mesoporous silica nanoparticles, and gold nanostructures radiolabelled with isotopes such as Zirconium-89, Gallium-68, and Iodine-124 have demonstrated high multimodal imaging capabilities with PET and SPECT. On the therapeutic side, radiolabelled nanoparticles with Rhenium-188, Yttrium-90, and Lutetium-177 have shown effective intra-tumoral retention and potential targeted therapeutic effects, reducing systemic toxicity compared to conventional treatments. Radiolabelled nanoparticles represent a significant advancement in the management of brain tumors, combining advanced diagnostics and targeted therapy in a theranostic approach. While preclinical results are promising, challenges remain regarding long-term safety, large-scale production, and regulatory approval for clinical application.

The rapid advancements in computer processing, algorithmic development, and the availability of large-scale datasets have positioned Artificial Intelligence (AI) as a valuable tool across multiple domains, including Medicine. In the field of Nuclear Medicine neuroimaging, with Positron Emission Tomography (PET), AI has demonstrated significant potential in improving diagnostic accuracy for neurodegenerative cognitive disorders. This is especially relevant for the early diagnosis, preclinical detection, and prediction of disease progression in Alzheimer’s disease (AD), the most prevalent form of cognitive impairment in individuals over 65 years of age. This narrative review aims to synthesize current advances, explore future directions, and highlight outstanding challenges in the application of Artificial Intelligence to PET imaging for the clinical management of Alzheimer’s disease, with particular focus on three key modalities: 18F-FDG PET, Amyloid PET, and Tau PET.

Background/Objectives: Recurrence prediction for patients with PC and tumor sizes ranging between 1 and 4 cm, classified as T1b and T2, remains a controversial problem. We evaluated which risk factors, identified during the primary tumor surgery, might play a prognostic role in predicting disease progression. Methods: We retrospectively enrolled 363 patients with classic PC who were in follow-up (207 T1b, 156 T2), with tissue risk factors at surgery in 209/363 cases. In all cases, an 131I-whole-body scan, SPECT/CT, and US were employed to detect any metastases during follow-up, and histology was used to confirm lesions. In the absence of surgery, metastases were validated by radioisotopic and radiologic procedures, eventually culminating in a needle biopsy and sequential thyroglobulin changes. Results: Metastases occurred in 61/363 (16.8%) patients (24 T1b, 37 T2). In 50/61 cases, the following risk factors were identified: minimal extrathyroid tumor extension (mETE) alone in 12/50 patients, neck lymph node (LN) metastases in 8/50 cases, and multifocality/multicentricity (M/M) in 6/50 cases. In the remaining 24/50 cases, the risk factors were associated with each other. From a Cox regression multivariate analysis, metastasis development was significantly (p < 0.001) influenced by only mETE and LN metastases, with a shorter disease-free survival (log-rank test). Conclusions: The current study proves that mETE and neck LN metastases are associated with aggressive PC. While LN metastasis’ role is known, mETE’s role is still being debated, and was removed by the AJCC’s eighth edition because it was considered to not be associated with an unfavorable prognosis. However, this interpretation is not supported by the present study and, according to comparable studies, we suggest a revision of the mETE classification be considered in the next AJCC edition.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28–5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

Background: Detecting pathological lymph nodes (LNs) is crucial for establishing the proper clinical approach in patients with head and neck cancer (HNC). Positron emission tomography with [18F] fluorodeoxyglucose (FDG PET) has high diagnostic value, although it can yield false positives since FDG-avid LNs can also occur from non-cancerous diseases. Objectives: To explore if radiomics features from FDG PET can enhance the identification of pathological lymph nodes in head and neck cancer. Materials and methods: This study was carried out on n=51 cervical lymph nodes (26 negative, 25 positive) from a cohort of n=27 subjects, and the standard of reference was fine needle aspiration cytology or excisional biopsy. An initial set of 54 IBSI-compliant radiomics features, which was subsequently reduced to 31 after redundancy elimination, was considered for the analysis. Mann–Whitney U tests were performed to compare each feature between positive and negative LNs. Classification models based on two sets of features, PETBase (SUVmax, MTV and TLG) and PETRad (radiomics features), respectively, were trained using logistic regression, support vector machines and Gaussian naïve Bayes, and their performance was compared. Accuracy was estimated via leave-one-out cross-validation. Results: We identified via univariate analysis 21 features that were statistically different between positive and negative LNs. In particular, dispersion features indicated that positive LNs had higher uptake non-uniformity than the negative ones. AUC, sensitivity, specificity and accuracy obtained with logistic regression were, respectively, 0.840, 68.0%, 89.5% and 80.4% for PETBase and 0.880, 72.0%, 90.0% and 82.4% for PETRad. The other classification models showed the same trend. Conclusions: Radiomics features from FDG PET can improve the diagnostic accuracy of LN status in HNC.

Introduction: Lung cancer (LC) is a leading cause of death among men and women, with non-small cell LC (NSCLC) accounting for a substantial portion of the histopathological spectrum and epidermal growth factor receptor (EGFR) mutations being correlated with its manifestation and evolution. Positron emission tomography (PET)/computed tomography has been the most widely used instrument to assess and monitor LC in a noninvasive way, including EGFR-mutated NSCLC, and its course during therapy, indicating to the referring physician the response to ongoing treatment or the lack of it. This systematic review aims to evaluate the feasibility and safety of radiolabeled EGFR tyrosine kinase inhibitors (TKis) in PET in clinical practice. Materials and Methods: From 1999 to April 2022 a Medline search was conducted on four different databases such as PubMed, Cochrane Library, Scopus, and Web of Sciences. Clinical studies were assessed by Quality Assessment of Diagnostic accuracy Studies-2 (QUADAS-2) and preclinical studies were also reported in this review. Results: Nine clinical studies were QUADAS-2 assessed and risk-of-bias assessment, and it turned out acceptable as two out of eight studies had low risk of bias in all four domains for risk-of-bias assessment, and the other four studies had three low-risk domains. The overall assessment for applicability risks was low. Conclusions: Radiolabeled EGFR-TKis in PET are a valid tool in identifying patients who may benefit from TKi therapy and who may not as a means to start an effective treatment. Although the number of clinical studies conducted so far is meager, these new PET tracers are already proving to be very useful in clinical settings as patient prognosis can be better assessed.

Background/Aim: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12–14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052–1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040–1.068, p < 0.001). Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Hashimoto’s thyroiditis (HT) is often associated with papillary thyroid carcinoma (PC); it is still a matter of controversy whether the behavior of carcinoma is more aggressive or not. During the follow-up, we retrospectively enrolled 97 patients with PC/HT after thyroidectomy without risk factors at the surgery of the primary tumor, such as multifocality/multicentricity, extrathyroid tumor extension, vascular invasion, neck and distant metastases, and aggressive histological variants. HT diagnosis was confirmed by histology and serum thyroid antibodies. Tumor size was ≤10 mm in 64 cases (microcarcinomas); 206 matched PC patients after thyroidectomy without HT and risk factors were enrolled as controls, totaling 122 microcarcinomas. During follow-up, metastases occurred in 15/97 (15.5%) PC/HT cases, eight microcarcinomas, and in 16/206 (7.8%) without HT, eight microcarcinomas (p = 0.04). Considering both PC/HT and PC patients without HT who developed metastases, univariate analysis showed an increased risk of metastases in patients with HT coexistence, OR: 2.17 (95% CI 1.03–4.60) p = 0.043. Disease-free survival (DFS) was significantly (p = 0.0253) shorter in PC/HT than in the controls. The present study seems to demonstrate that HT is not a cancer protective factor in PC patients given the less favorable outcomes and significantly shorter DFS. HT may also represent an independent recurrence predictor without other risk factors.