Francesco Bertagna's research while affiliated with Università degli Studi di Brescia and other places

Purpose Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging. Methods Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [¹⁸F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [⁶⁸Ga]Ga-PSMA-11, [¹⁸F]DCFPyL, [¹⁸F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [¹⁸F]PSMA-1007. The average maximum Standardized Uptake Value (SUVmax) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases. Conclusions Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings.

Simple Summary Richter transformation (RT) is characterized by the transformation of CCL in the aggressive lymphoma variant with a significant worsening in prognosis. Initial reports about a substantial impact of 2-deoxy-2-[¹⁸F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) in predicting RT are available in the literature. Using data from 15 published studies, including 1593 CLL patients, we demonstrated that 2-[¹⁸F]FDG uptake expressed as the maximum standardized uptake value (SUVmax) has a high negative predictive value. Abstract Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[¹⁸F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[¹⁸F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.

Objective Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated the possible relationship between retinal microcirculation, positron emission tomography myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi) Design and method Nineteen hypertensive patients (mean age 65 ± 11, 10 F) without flow-limiting epicardial coronary artery disease underwent patients wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera, echocardiography, including MEEi computation, and cardiac 13NH3 positron emission tomography (13NH3 PET) with assessment of myocardial coronary flow reserve (CFR). A positive 13NH3 PET was defined as a ratio of stress (regadenoson) myocardial blood flow (MBF)/mass and resting MBF/mass lower than 2. Results No significant differences of demographic parameters were observed between patients with positive (n=6) vs negative (n=13) 13NH3 PET. In all patients WLR was significantly related to BMI (0,50, p=0.02), age (r=0.49, p=0.03)and LVMi (r=0.48, p=0.03) at univariate analysis. A negative correlation was also observed between WLR and total CFR (-0.64, p=0.003) and MMEi (-0.35, p=0.13). The relationship between WLR and CFR remained significant after adjustment for age and BMI (r=-0.49, p=0.047). Conclusions In hypertensive patients without flow-limiting epicardial coronary artery disease, retinal WLR could reflect the presence of structural alterations in coronary microcirculation, possibly contributing to an impairment of CFR and to early LV dysfunction, as detected by low values of MEEi.

Background Several recent studies have proposed the possible application of positron emission tomography/computed tomography (PET/CT) administering radiolabelled fibroblast-activation protein (FAP) inhibitors for various forms of thyroid cancer (TC), including differentiated TC (DTC), and medullary TC (MTC). Methods The authors conducted an extensive literature search of original studies examining the effectiveness of FAP-guided PET/CT in patients with TC. The papers included were original publications exploring the use of FAP-targeted molecular imaging in restaging metastatic DTC and MTC patients. Results A total of 6 studies concerning the diagnostic yield of FAP-targeted PET/CT in TC (274 patients, of which 247 DTC and 27 MTC) were included in this systematic review. The included articles reported high values of FAP-targeted PET/CT detection rates in TC, ranging from 81 to 100% in different anatomical sites and overall superior to the comparative imaging method. Conclusion Although there are promising results, the existing literature on the diagnostic accuracy of FAP-guided PET in this context is still quite limited. To thoroughly evaluate its potential significance in TC patients, it is needed to conduct prospective randomized multicentric trials.

Simple Summary The prognosis of prostate cancer (PCa) patients and their best therapeutic approach are related to the risk-based classification of this neoplasm since subjects with higher risk could have a higher incidence of recurrence. In addition, patients with low- and intermediate-risk PCa could benefit from active surveillance (AS). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging has demonstrated its value for the assessment, prognostic role, and ability to guide the therapy of PCa. The aim of this systematic review was to assess the role of PSMA PET in guiding the correct classification of low-to-intermediate risk PCa subjects and the AS approach. Insights on the value of this imaging modality in these settings have emerged; however, further research in this field is necessary to clearly define the role of PSMA PET. Abstract Background: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients. Methods: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles. Results: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS. Conclusion: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.

Diffuse Large B‐Cell Lymphomas (DLCBL) and mucosa‐associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and has a poorer prognosis. The aim of this retrospective study was to explore the role of fluorine‐18‐fluorodeoxyglucose positron emission tomography/computed tomography (2‐[ ¹⁸ F]‐FDG‐PET/CT) and radiomics features (RFs) in predicting the final diagnosis of patients with PGLs. Ninety‐one patients with newly diagnosed PGLs who underwent pre‐treatment 2‐[ ¹⁸ F]‐FDG‐PET/CT were included. PET images were qualitatively and semi‐quantitatively analyzed by deriving maximum standardized uptake value body weight (SUVbw), maximum standardized uptake value lean body mass (SUVlbm), maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L‐L SUV R), lesion to blood‐pool SUVmax ratio (L‐BP SUV R), metabolic tumor volume (gMTV) and total lesion glycolysis of gastric lesion (gTLG), total MTV (tMTV), TLG, and first‐order RFs (histogram‐related and shape related). Receiver‐operating characteristic (ROC) curve analyses were performed to determine the differential diagnostic values of PET parameters. The final diagnosis was DLBCL in 54 (59%) cases and MALT in 37 cases (41%). PGLs showed FDG avidity in 83 cases (90%), 54/54 of DLBCL and 29/37 of MALT. All PET/CT metabolic features, such as stage of disease and tumor size, were significantly higher in DLBCL than MALT; while the presence of H. Pylori infection was more common in MALT. At univariate analysis, all PET/CT metrics were significantly higher in DLBCL than MALT lymphomas, while among RFs only Shape volume_vx and Shape sphericity showed a significant difference between the two groups. In conclusion we demonstrated that 2‐[ ¹⁸ F]‐FDG‐PET/CT parameters can potentially discriminate between DLBCL and MALT lymphomas with high accuracy. Among first‐order RFs, only Shape volume_vx and Shape sphericity helped in the differential diagnosis.

This retrospective study investigated the prognostic role of disease dissemination features (Dmax and Dmaxbsa) measured by 2-[18F]FDG PET/CT in newly diagnosed Burkitt Lymphoma (BL) patients, comparing their performance with other metabolic parameters. We included 78 patients diagnosed with BL between 2010 and 2022 with an available baseline PET, interim PET/CT (iPET) and end of treatment PET/CT (eotPET) and with a minimum of two 2-[18F]FDG avid lesions present at the baseline scan. Dmax was calculated from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) by using LIFEx software; Dmaxbsa was calculated as Dmax normalized for body surface area according to the Du Bois method. We evaluated their effect on metabolic treatment response evaluated by PET, on progression free survival (PFS) and on overall survival (OS). Dmaxbsa was significantly associated with tumor stage, bulky and extranodal disease, MTV and TLG. At a median follow-up of 49 months, the median PFS and OS were 45 and 48 months. Dmax and Dmaxbsa were significantly higher in not complete metabolic response than complete metabolic response group at iPET and eotPET.As far as PFS, parameters including iPET/CT, eotPET/CT outcomes, MTV and TLG showed to be independent prognostic factors while Dmax and Dmaxbsa were not significantly associated with the outcome. Dissemination features, together with eotPET/CT results, MTV and TLG, demonstrated to be significantly correlated with OS. In conclusion, in this study we demonstrated that dissemination features derived by 2[18F]-FDG PET/CT were significantly correlated with response to treatment and long-term outcome, independently from other PET features.

Purpose The management of differentiated thyroid cancer (DTC) is actually based on a dynamic risk stratification based on classes of response to the therapy. Indeterminate response (IR) includes a heterogeneous group of patients with different characteristics, particularly different Tg and AbTg levels and/or imaging findings. The aim of systematic review (SR) is to evaluate the prognosis, diagnostic findings and other characteristics of patients in the IR class. Methods A wide literature search in the Scopus, PubMed/MEDLINE and Web of Science databases was performed to find published articles on patients with DTC and IR after treatment. The quality assessment of studies was carried out using QUADAS-2 evaluation. Results Eight articles were included in the systematic review. Six studies evaluated the prognosis and the prognostic factor in patients with IR, one study evaluated the role of 2-[¹⁸F]FDG PET-CT in the management of patients with IR and biochemical incomplete response and one study the risk factors for IR. Conclusion Patients with DTC and IR to therapy have a probability of disease relapse < 15%. Tg value could be a predictor of disease progression. The role of 2-[¹⁸F]FDG PET-CT needs to be further investigated.