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Immuno-PET/CT imaging, a branch of molecular imaging, can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is a pan-cancer biomarker and plays a crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop and translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use. Methods: Two sdAbs (i.e., His-tagged T4 and His-tag-free RT4) are recombinantly expressed in Chinese hamster ovary cells. The purities and binding kinetics are determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, high-performance liquid chromatography, and surface plasmon resonance assays. The AlF restrained complexing agent (RESCA) method is applied to develop 18 F-labeled sdAb tracers ([ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4), followed by thorough preclinical imaging and blocking studies on tumor-bearing mice and a pilot clinical trial evaluating the clinical imaging safety and feasibility of [ 18 F]AlF-RESCA-T4 immuno-PET/CT. Results: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical imaging in the T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) of [ 18 F]AlF-RESCA-T4 (11.13 ± 1.53, n = 4) and [ 18 F]AlF-RESCA-RT4 (8.83 ± 1.22, n = 4), which were significantly reduced by coinjection of unlabeled T4 and RT4 in blocking studies. The His-tag removal strategy further optimized the probe's in vivo pharmacokinetics and reduced renal radioactivity accumulation without significantly decreasing tumor uptake. In a pilot clinical trial, [ 18 F]AlF-RESCA-T4 immuno-PET/CT showed promising potency in annotating Trop2 expression and differentiating tumors from inflammatory diseases such as tuberculosis. Conclusion: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 can specifically annotate Trop2 expression. Clinical [ 18 F]AlF-RESCA-T4 immuno-PET/CT imaging can screen patients for Trop2-targeted therapies and differentiate lung inflammation from cancer., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Although many well-known factors affect the maximum standardized uptake value (SUVmax), it remains the most requested and used parameter, especially among clinicians, despite other parameters, such as the standardized uptake value corrected for lean body mass and the metabolic tumor volume, being proven to be less sensitive to the same factors, more robust, and eventually more informative. This study intends to provide robust evidence regarding the diagnostic and prognostic value of SUVmax in a large cohort of subjects with suspected malignant lung nodules imaged by [ 18 F]FDG PET/CT., Materials and Methods: We performed a retrospective analysis of patients with suspected/confirmed primary lung tumours undergoing [18F]FDG PET/CT. The sample size was 567 patients. Demographics, imaging, surgical, histological, and follow-up data were collected. SUVmax was analysed according to histology, stage, scanner, and outcome. The impact on measured values of different reconstruction protocols was assessed. All potential predictors of patients' outcome were assessed., Results: 91% cases were primary lung tumours. Lung benign nodules or metastases accounted for 5% and 4% of cases. Most patients presented with adenocarcinoma (70%) and stage I disease (51%); 144 patients relapsed and 55 died. SUVmax failed to effectively differentiate benign lesions from primary tumours or metastases. Stage I patients presented lower SUVmax. SUVmax significantly correlated with patient weight, injected [ 18 F]FDG activity, and lesion size and differed between reconstructions' protocols. Survival analyses revealed no independent prognostic significance for SUVmax in progression-free after adjusting for other variables. SUVmax correlated with overall survival, disease stage and tumour histotype., Conclusion: Our study confirms that SUVmax, though widely employed, present relevant limitations in discriminating between benign lesion and lung cancer, in classifying cancer histotypes, and in predicting patient outcomes independently. Known influencing factors significantly impact on numerical values, thus SUV values should be regarded with caution in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The Ethics Committee of IRCCS Humanitas Research Hospital approved the study (approval number 3/18, on 17 April 2018, protocol ADVIMAG-Thorax). Consent to participate: A specific informed consent was waived because of the observational and retrospective study design. Competing interests: AC is editor-in-chief of EJNMMI. MK, LA and MS are in the editorial board of EJNMMI. MK and MS are section editors of the Artificial intelligence, machine learning and radiomics section of Cancer Imaging. AC reports personal fees from AmGen, General Electric Healthcare, Novartis, Sirtex, and Telix, all outside the submitted work. All other authors did not report competing interest., (© 2024. The Author(s).)

Purpose: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was able to demonstrate a persistent inflammatory process. Methods: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [18F]FDG positron emission tomography/computed tomography ([18F]FDG-PET/CT). Whole-body [18F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [18F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses. Results: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46–80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [18F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [18F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls. Conclusion: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms. [ABSTRACT FROM AUTHOR]