Laura Evangelista

Purpose of review: Gliomas remain associated with poor outcomes, despite multimodal treatment. Response assessment relies primarily on MRI; however, treatment-related changes (TRC), particularly pseudoprogression (psPD), may mimic tumor progression disease (PD), creating a major diagnostic challenge. This review focuses on studies published over the past 18 months addressing the role of molecular PET imaging in differentiating TRC from PD in gliomas, highlighting developments with potential implications for clinical practice. Recent findings: Recent evidence emphasizes the increasingly complementary role of molecular PET in glioma response assessment. Static amino acid PET, particularly [ ¹⁸ F]FET, may provide diagnostic information comparable to dynamic acquisition while simplifying protocol acquisition, although evidence remains heterogeneous and retrospective. Beyond amino acid tracers, [ ⁶⁸ Ga]FAPI PET may provide complementary information on tumor microenvironment and presents an emerging research direction. Increasing use of quantitative PET parameters has also highlighted the impact of reconstruction algorithms, reference regions and segmentation strategies on quantitative biomarkers and diagnostic thresholds. Artificial intelligence, radiomics and automated segmentation may further improve the integration of multimodal and quantitative assessment. Summary: Molecular PET imaging provides clinically relevant complementary information to conventional MRI in the assessment of TRC, including psPD. Recent evidence highlights three complementary directions: simpler acquisition protocols, greater standardization of quantitative assessment and integration of complementary biological information. Future prospective multicenter studies are needed to establish the optimal timing and role of repeated PET examinations, validate emerging tracers, quantitative biomarkers and artificial intelligence based approaches, determining their impact on patient outcomes.

An 81-year-old man with biopsy-proven high-risk prostate cancer (PCa) underwent staging with [ ¹⁸ F]piflufolastat PET/CT. Imaging showed intense uptake in the prostate gland and an incidental PSMA-avid pleural lesion in the right costophrenic recess. A surgical resection of the pleural lesion was performed, revealing a well-circumscribed spindle-cell mesenchymal proliferation consistent with a solitary fibrous tumor of pleura (SFTP).

Background: Testicular germ cell tumours (TGCTs) are the most common malignancy in young adult males. After chemotherapy, the evaluation of residual masses is critical. However, the current standard imaging modality, [ ¹⁸ F]-FDG PET, has limited specificity—particularly in distinguishing viable tumour from necrosis or mature teratoma. This limitation often leads to unnecessary surgery or misinterpretation of treatment response. Objectives: This systematic review aims to explore and evaluate novel PET tracers that could improve diagnostic accuracy in TGCTs, especially in post-chemotherapy settings. Methods: A comprehensive literature search was conducted on PubMed and Scopus through December 2025, using terms including “testicular,” “germ cell tumour,” “PET scan,” and “novel.” Studies focusing solely on [ ¹⁸ F]-FDG were excluded. Preclinical studies, case reports, and clinical trials investigating alternative PET tracers or relevant molecular targets (e.g., ghrelin, claudin-6) were included. The quality of selected articles was assessed by using CASP for the qualitative research. Results: A total of 17 studies met the inclusion criteria. Emerging PET tracers evaluated include [ ¹⁸ F]-FLT, FAPI, αvβ3-integrin-targeted agents, [ ¹⁸ F]-fluciclovine, PSMA-targeted tracers, and those based on ghrelin and claudin-6. Among these, αvβ3-targeted imaging has shown promising preclinical results in differentiating mature teratoma from necrosis. Ghrelin receptor tracers appear promising due to their high expression in TGCTs, although they remain in preclinical development. Claudin-6, a tight-junction protein, is highly expressed in most TGCT histologies and may be a viable molecular target, as supported by early-phase clinical trials. Conclusions: Novel PET tracers represent a promising avenue to refine TGCT management. αvβ3-integrin and ghrelin-based tracers are particularly noteworthy for their potential to guide decision-making after chemotherapy. However, further clinical validation is required before routine implementation. These innovations could significantly reduce overtreatment and enhance personalized care in TGCT patients.

Background: Breast cancer (BC) is a biologically heterogeneous disease, with molecular subtypes differing fundamentally in terms of aggressiveness, metabolic behavior, and therapeutic response. Conventional ¹⁸F-FDG PET provides semi-quantitative assessment of glucose-analogue uptake using the standardized uptake value (SUV), whereas dynamic PET with Patlak analysis can estimate kinetic parameters such as the net influx rate constant (K_i) and the volume of distribution (V_d). However, the interpretation of these parameters in breast tissue remains insufficiently defined, and data across BC subtypes are limited. This proof-of-concept study explored the feasibility of deriving preliminary reference ranges for non-pathological breast tissue and describing subtype-specific patterns of kinetic parameters. Methods: Six breast cancer patients affected by Luminal (n = 4) or triple negative BC (TNBC, n = 3) and six control patients underwent dynamic ¹⁸F-FDG PET/CT. Patlak kinetic analysis generated parametric K_i and V_d maps. Lesion-level first-order radiomics features were extracted for each breast lesion. Non-lesional breast volumes (contralateral breast and breast excluding disease) were characterized to derive exploratory physiological reference ranges. Results: In control whole-breast tissue, median values were SUV 0.28 g/mL, K_i 0.056 mL/min/100 mL, and V_d ~9%. Non-lesional breast tissue in BC remained statistically concordant with controls. Lesion analysis suggested a possible metabolic gradient across subtypes: Luminal B with low proliferation activity exhibited lowest K_i (0.34 mL/min/100 mL), and highest V_d (~39%); Luminal A showed intermediate K_i (1.93 mL/min/100 mL) and V_d (~27%) values; TNBC showed higher K_i (3.02 mL/min/100 mL) with a greater proportion of zero-valued V_d voxels. Conclusions: This exploratory study suggests that parametric maps may be feasible for describing physiological breast tissue kinetic ranges and for exploring subtype-associated metabolic differences in BC. The observed K_i and V_d patterns may reflect differences in glucose phosphorylation and tracer distribution across tumor phenotypes, but the biological meaning of Patlak-derived parameters requires further methodological and histopathological validation. Larger prospective studies are needed before these parameters can be considered clinically applicable imaging biomarkers.

This review aims to summarize and critically evaluate published clinical trials investigating the role of [¹⁸F]FDG PET in bladder cancer (BC) management, and to provide an overview of ongoing trials in this field. A literature search was conducted in PubMed up to 31 August 2025 and on ClinicalTrials.gov to identify clinical trials assessing the role of [¹⁸F]FDG PET/CT in patients with BC. The search strategy used the terms "FDG PET," "bladder cancer," "PET/CT," "clinical trials," and "PET/MRI." Review articles, editorials, letters, comments, and case reports were excluded. Two investigators independently screened the literature, and additional trial information was retrieved from ClinicalTrials.gov. Five eligible full-text publications and eight registered clinical trials were identified. Among the publications, two reported study protocols, two were pilot studies, and one was an ancillary analysis from a larger trial. In addition, eight ongoing clinical trials were retrieved from ClinicalTrials.gov. Available data suggest that [¹⁸F]FDG PET/MRI may be more suitable than PET/CT for evaluating primary bladder lesions, while PET/CT is particularly effective in detecting distant metastases. Several ongoing studies are also investigating delayed acquisition protocols to improve detection of nodal metastases. [¹⁸F]FDG PET/CT and PET/MRI show promise for enhancing local and distant staging in muscle-invasive bladder cancer, although their role in nodal evaluation remains uncertain. Current evidence is limited by heterogeneous study designs, small patient cohorts, and the lack of standardized imaging protocols.

Background: Prostate cancer (PCa) is biologically heterogeneous, requiring management strategies that balance oncologic benefit with preservation of quality of life. Prostate-specific membrane antigen (PSMA) has emerged as a key theranostic biomarker enabling highly sensitive molecular imaging and targeted therapy. Purpose: The present manuscript aims to summarize the clinical role of PSMA-PET/CT in PCa across staging, treatment selection, and response assessment, with a special focus on its contribution to personalized management. Key Findings: PSMA-PET/CT demonstrates superior accuracy compared with conventional imaging, frequently leading to stage migration and changes in therapeutic strategy. It improves detection of metastatic and recurrent disease, guides selection for systemic and PSMA-targeted therapies, and supports metastasis-directed treatment in oligometastatic settings, potentially delaying androgen-deprivation therapy and preserving quality of life. Additionally, PSMA-PET enhances intra-prostatic lesion delineation for focal therapies and radiotherapy planning. Limitations include reduced sensitivity for very small lesions, possible false positives, variability among tracers, and issues related to access and standardization. Conclusions: PSMA-PET/CT is a cornerstone of precision imaging in PCa, enabling more individualized treatment decisions across the disease continuum. Ongoing studies will further define its long-term clinical impact and integration into routine care.

Purpose Differentiating malignant from inflammatory uptake on ¹⁸F-FDG PET/CT remains a major diagnostic challenge, as standardised uptake value (SUV) lacks specificity. This study evaluated whether parametric imaging from short-duration dynamic FDG PET/CT provides complementary information beyond SUV for distinguishing malignancy from inflammation. Methods Twenty-eight patients undergoing oncologic PET/CT (breast, lung, lymphatic or gastrointestinal cancer) were included, yielding 68 lesions (43 malignant, 25 inflammatory). Short dynamic acquisitions (20 min) were motion-corrected and used to generate influx rate (Ki) and distribution volume (Vd) maps. Lesions were segmented on SUV images (40% SUVmax), and radiomic features were extracted from SUV, Ki, and Vd maps, including core and peritumoral regions. Classification performance was assessed both using logistic regression and Random Forest model. Results Malignant lesions exhibited higher mean values than inflammatory lesions for both SUV (6.0 vs. 2.7 g/ml) and Ki (2.0 vs. 0.8 ml/min/100 ml), while Vd values largely overlapped between classes (50 vs. 47%). No single parameter provided a reliable discriminative threshold. Restricting the analysis to equivocal SUV values (< 5.2 g/ml), multivariate regression combining SUV Mean, Ki/Vd Variance, and Ki Entropy achieved an accuracy of 0.86 (pseudo-R² = 0.42), outperforming SUV Mean alone (accuracy 0.77, pseudo-R² = 0.26). Core–peritumoral analysis revealed as Ki/Vd Variance the most statistically significant features between the two classes (4.35 ± 3.36 malignant vs. 1.93 ± 1.34 inflammatory; p = 0.006). Random Forest classification confirmed superior performance of parametric features (ROC AUC 0.86 ± 0.10) compared with SUV-only models (0.83 ± 0.08). Conclusion Short dynamic Patlak FDG PET/CT improves differentiation of malignant from inflammatory uptake beyond SUV alone. Decomposing FDG uptake into metabolised (Ki) and unmetabolised (Vd) fractions, components provide physiologically meaningful insights, revealing steeper core-to-peritumoral metabolic gradients in malignancy and more homogeneous tracer distribution in inflammation. These findings support the added value of parametric imaging and motivate prospective validation in larger clinical cohorts. Graphical Abstract The alternative text for this image may have been generated using AI. Graphical abstract of short-dynamic Patlak parametric 18F-FDG PET/CT for differentiating malignant from inflammatory lesions. Conventional PET metrics, including SUV, Ki, and Vd considered individually, did not provide a reliable threshold for lesion classification because of substantial intercorrelation between features, particularly between mean SUV and Ki. The most informative biomarkers were derived from the metabolic relationship between the lesion core and the peritumoral rim. In particular, Ki/Vd-based core–rim features, reflecting the balance between metabolic trapping and membrane washout, demonstrated strong potential for capturing spatial metabolic heterogeneity and improving discrimination between malignancy and inflammation.