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Background: [ 18 F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [ 18 F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up., Results: 110 patients referred for baseline and follow-up standard digital [ 18 F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTC UHD or EARL2 or PERCIST UHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients., Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [ 18 F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory., (© 2024. The Author(s).)

Purpose: Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre., Materials and Methods: The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelial ovarian cancer and for whom peritoneal histological samples were available in the tumour bank. Immunodetection of PSMA was performed to assess its cellular and neovascular expression. Slides were controlled by a certified pathologist, recorded as tiled tiff images and processed to compute the proportion of DAB stained surface., Results: Of the 51 patients identified by the database screening, 32 patients were included resulting in 57 samples (32 pre-chemotherapy and 25 post-chemotherapy histological samples). Nine patients were chemo-sensitive, 10 were partially chemo-sensitive and 13 were chemo-resistant/refractory. In the entire dataset, the expression of PSMA was quasi-inexistent: %DAB PSMA  = 0.04 (± 0.12) %. There was no significant difference in the %DAB PSMA of sensitive, partially sensitive and resistant/refractory patients. There was also no significant difference in %DAB PSMA in tumours before and after chemotherapy in the 25 patients for whom both samples were available., Conclusion: The present work demonstrates that PSMA expression is negligible and a fortiori non-sufficient to ensure its usefulness as a prognosticator or a target for a theranostic strategy in ovarian cancers.

Background: Anal cancer is a relatively rare tumor of which incidence increases in developed countries. 18 F-FDG PET has been increasingly used for its post radio-chemotherapy evaluation. However, several authors have reported the risk of local false-positive findings leading to low specificity and positive predictive values. These false-positive results could be due to post-radiotherapy inflammation or infection but certainly also to physiological anal canal uptake that is observed on a regular basis in clinical practice. The purpose of this prospective study (NCT03506529; HYPHYCA) was therefore to seek predictive factors of physiological anal canal hypermetabolism., Materials and Methods: Over a 2-month period, patients aged 18 years old and more, referred for 18 F-FDG PET-CT at two EARL-accredited PET centers were included, after obtaining their informed and written consent. They were asked to fill in a questionnaire including seven closed questions about usual intestinal transit, ongoing medications relative to intestinal transit, history of digestive, and anal and/or pelvic diseases. Age, gender, and body mass index (BMI) were recorded. A single nuclear medicine physician visually and quantitatively analyzed anal canal uptake (SUV max&#95;EARL ) and assessed visual rectal content (air, feces, or both) and the largest rectal diameter (mm)., Results: Six hundred and thirteen patients were included (sex ratio F/M = 0.99) and 545 (89%) questionnaires were entirely completed. Significantly more males presented anal canal hypermetabolism (sex ratio (M/F) = 1.18 versus 0.85, p = 0.048). Moreover, patients with anal canal hypermetabolism had higher BMI (27.6 (5.7) kg/m 2 versus 23.9 (4.5) kg/m 2 , p < 0.0001), higher rate of hemorrhoid history (43% versus 27%, p = 0.016), and higher rate of rectum filled with only feces (21% versus 12%, p = 0.019) as compared to patients with no anal canal uptake. On logistic regression, all these variables were found to be independent predictors of the occurrence of an anal canal hypermetabolism. Odds ratio were 1.16 (1.12-1.20) per unit of BMI (kg/m 2 ) (p < 0.0001), 1.48 (1.04-2.11) for males (p = 0.030), 1.64 (1.10-2.45) for hemorrhoids history (p = 0.016), and 1.94 (1.147-3.22) for the rectum filled with only feces (p = 0.010)., Conclusion: According to our study, the predictive factors of physiological anal canal hypermetabolism are high BMI, male gender, hemorrhoid history, and rectum filled with only feces. This may pave the way to a more specific interpretation of post radio-chemotherapy PET evaluations of anal canal cancer, provided that other studies are conducted in this specific population., Trial Registration: This prospective study was registered at Clinicaltrial.gov: NCT03506529; HYPHYCA on April 24, 2018.

Aims: (1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18 F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring., Materials and Methods: Retrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed., Results: Mean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation&#95; BONE ), liver (%Variation&#95; LIVER ) and spleen (%Variation&#95; SPLEEN ) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation&#95; LIVER and %Variation&#95; SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation&#95; BONE , %Variation&#95; LIVER , and %Variation&#95; SPLEEN . On the contrary, %Variation&#95; BONE and %Variation&#95; SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = - 0.342 (p = 0.010) and ρ = - 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmax EARL . %Variation&#95; LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmax EARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk., Conclusions: Neither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring.

Background: The aim of this study is to determine if the choice of the 18 F-FDG-PET protocol, especially matrix size and reconstruction algorithm, is of importance to discriminate between immunohistochemical subtypes (luminal versus non-luminal) in breast cancer with textural features (TFs)., Procedures: Forty-seven patients referred for breast cancer staging in the framework of a prospective study were reviewed as part of an ancillary study. In addition to standard PET imaging (PSF WholeBody ), a high-resolution breast acquisition was performed and reconstructed with OSEM and PSF (OSEM breast /PSF breast ). PET standard metrics and TFs were extracted. For each reconstruction protocol, a prediction model for tumour classification was built using a random forests method. Spearman coefficients were used to seek correlation between PET metrics., Results: PSF WholeBody showed lower numbers of voxels within VOIs than OSEM breast and PSF breast with median (interquartile range) equal to 130 (43-271), 316 (167-1042), 367 (107-1221), respectively (p < 0.0001). Therefore, using LifeX software, 28 (59%), 46 (98%) and 42 (89%) patients were exploitable with PSF WholeBody , OSEM breast and PSF breast , respectively. On matched comparisons, PSF breast reconstruction presented better abilities than PSF wholeBody and OSEM breast for the classification of luminal versus non-luminal breast tumours with an accuracy reaching 85.7% as compared to 67.8% for PSF wholeBody and 73.8% for OSEM breast . PSF breast accuracy, sensitivity, specificity, PPV and NPV were equal to 85.7%, 94.3%, 42.9%, 89.2%, 60.0%, respectively. Coarseness and ZLNU were found to be main variables of importance, appearing in all three prediction models. Coarseness was correlated with SUV max on PSF wholeBody images (ρ = - 0.526, p = 0.005), whereas it was not on OSEM breast (ρ = - 0.183, p = 0.244) and PSF breast (ρ = - 0.244, p = 0.119) images. Moreover, the range of its values was higher on PSF breast images as compared to OSEM breast , especially in small lesions (MTV < 3 ml)., Conclusions: High-resolution breast PET acquisitions, applying both small-voxel matrix and PSF modelling, appeared to improve the characterisation of breast tumours.

Background: The clinical validation of the EARL harmonization program for standardised uptake value (SUV) metrics is well documented; however, its potential for defining metabolic active tumour volume (MATV) has not yet been investigated. We aimed to compare delineation of MATV on images reconstructed using conventional ordered subset expectation maximisation (OSEM) with those reconstructed using point spread function modelling (PSF-reconstructed images), and either optimised for diagnostic potential (PSF) or filtered to meet the EANM/EARL harmonising standards (PSF 7 )., Methods: Images from 18 stage IIIA-IIIB lung cancer patients were reconstructed using all the three methods. MATVs were then delineated using both a 40% isocontour and a gradient-based method. MATVs were compared by means of Bland-Altman analyses, and Dice coefficients and concordance indices based on the unions and intersections between each pair of reconstructions (PSF vs OSEM, PSF 7 vs PSF and PSF 7 vs OSEM)., Results: Using the 40% isocontour method and taking the MATVs delineated on OSEM images as a reference standard, the use of PSF 7 images led to significantly higher Dice coefficients (median value = 0.96 vs 0.77; P < 0.0001) and concordance indices (median value = 0.92 vs 0.64; P < 0.0001) than those obtained using PSF images. The gradient-based methodology was less sensitive to reconstruction variability than the 40% isocontour method; Dice coefficients and concordance indices were superior to 0.8 for both PSF reconstruction methods. However, the use of PSF 7 images led to narrower interquartile ranges and significantly higher Dice coefficients (median value = 0.96 vs 0.94; P = 0.01) and concordance indices (median value = 0.89 vs 0.85; P = 0.003) than those obtained with PSF images., Conclusion: This study demonstrates that automatic contouring of lung tumours on EARL-compliant PSF images using the widely adopted automatic isocontour methodology is an accurate means of overcoming reconstruction variability in MATV delineation. Although gradient-based methodology appears to be less sensitive to reconstruction variability, the use of EARL-compliant PSF images significantly improved the Dice coefficients and concordance indices, demonstrating the importance of harmonised-images, even when more advanced contouring algorithms are used.

Background: Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment., Methods: In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification., Results: Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter-observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (ρ c = 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and -1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05)., Conclusions: Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur.

Background: The use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT)., Methods: Firstly, a NEMA NU 4-2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media., Results: There was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4-2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (-0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004)., Conclusions: The use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4-2008 IQ parameters.