[18F]FDG-PET/CT atypical response patterns to immunotherapy in non-small cell lung cancer patients: long term prognosis assessment and clinical management proposal.

AIM: To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). METHODS: 109 patients were prospectively included and underwent [18F]FDG-PET/CT at baseline, after 7 weeks (PETinterim1), and 3 months (PETinterim2) of treatment. On PETinterim1, tumor response was assessed using standard PERCIST criteria. In the event of PERCIST progression at this time-point, the study design provided for continued immunotherapy for 6 more weeks. Additional response patterns were then considered on PETinterim2: pseudo-progression (PsPD, subsequent metabolic response); dissociated response (DR, coexistence of responding and non-responding lesions), and confirmed progressive metabolic disease (cPMD, subsequent homogeneous progression of lesions). Patients were followed up for at least 12 months. RESULTS: Median follow-up was 21 months. At PETinterim1, PERCIST progression was observed in 60% (66/109) of patients and ICPI was continued in 59/66. At the subsequent PETinterim2, 14% of patients showed PsPD, 11% DR, 35% cPMD, and 28% had a sustained metabolic response. Median overall survival (OS) and progression-free-survival (PFS) did not differ between PsPD and DR (27 vs 29 months, p = 1.0; 17 vs 12 months, p = 0.2, respectively). The OS and PFS of PsPD/DR patients were significantly better than those with cPMD (29 vs 9 months, p < 0.02; 16 vs 2 months, p < 0.001), but worse than those with sustained metabolic response (p < 0.001). This 3-group prognostic stratification enabled better identification of true progressors, outperforming the prognostic value of standard PERCIST criteria (p = 0.03). CONCLUSION: [18F]FDG-PET/CT enables early assessment of response to immunotherapy. The new wsPERCIST ("wait and see") PET criteria proposed, comprising immune-related atypical response patterns, can refine conventional prognostic stratification based on PERCIST criteria. TRIAL REGISTRATION: HDH F20230309081206. Registered 20 April 2023. Retrospectively registered.

Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study.

BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.

Development and validation of a radiomic model for the diagnosis of dopaminergic denervation on [18F]FDOPA PET/CT.

PURPOSE: FDOPA PET shows good performance for the diagnosis of striatal dopaminergic denervation, making it a valuable tool for the differential diagnosis of Parkinsonism. Textural features are image biomarkers that could potentially improve the early diagnosis and monitoring of neurodegenerative parkinsonian syndromes. We explored the performances of textural features for binary classification of FDOPA scans. METHODS: We used two FDOPA PET datasets: 443 scans for feature selection, and 100 scans from a different PET/CT system for model testing. Scans were labelled according to expert interpretation (dopaminergic denervation versus no dopaminergic denervation). We built LASSO logistic regression models using 43 biomarkers including 32 textural features. Clinical data were also collected using a shortened UPDRS scale. RESULTS: The model built from the clinical data alone had a mean area under the receiver operating characteristics (AUROC) of 63.91. Conventional imaging features reached a maximum score of 93.47 but the addition of textural features significantly improved the AUROC to 95.73 (p < 0.001), and 96.10 (p < 0.001) when limiting the model to the top three features: GLCM_Correlation, Skewness and Compacity. Testing the model on the external dataset yielded an AUROC of 96.00, with 95% sensitivity and 97% specificity. GLCM_Correlation was one of the most independent features on correlation analysis, and systematically had the heaviest weight in the classification model. CONCLUSION: A simple model with three radiomic features can identify pathologic FDOPA PET scans with excellent sensitivity and specificity. Textural features show promise for the diagnosis of parkinsonian syndromes.

Prognostic value of immunotherapy-induced organ inflammation assessed on 18FDG PET in patients with metastatic non-small cell lung cancer.

PURPOSE: We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 18FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). METHODS: Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. 18FDG PET/CT exams were performed at baseline (PETBaseline) and repeated after 7-8 weeks (PETInterim1) and 12-16 weeks (PETInterim2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ 18FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected. RESULTS: Exploratory cohort (Nice, France): PETInterim1 and PETInterim2 revealed the occurrence of at least one ICPI-induced organ inflammation in 72.8% of patients, including midgut/hindgut inflammation (33.7%), gastritis (21.7%), thyroiditis (18.5%), pneumonitis (17.4%), and other organ inflammations (9.8%). iPERCIST tumor response was associated with improved progression-free survival (p < 0.001). iPERCIST tumor response and immuno-induced gastritis assessed on PET were both associated with improved overall survival (OS) (p < 0.001 and p = 0.032). Combining these two independent variables, we built a model predicting patients' 2-year OS with a sensitivity of 80.3% and a specificity of 69.2% (AUC = 72.7). Validation cohort (Genova, Italy): Immuno-induced gastritis (19.6% of patients) was associated with improved OS (p = 0.04). The model built previously predicted 2-year OS with a sensitivity and specificity of 72.0% and 63.6% (AUC = 70.7) and 3-year OS with a sensitivity and specificity of 69.2% and 80.0% (AUC = 78.2). CONCLUSION: Immuno-induced gastritis revealed by early interim 18FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.

EANM practice guideline/SNMMI procedure standard for dopaminergic imaging in Parkinsonian syndromes 1.0.

PURPOSE: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. METHODS: Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. CONCLUSION: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

Correction to: 18F-DOPA PET/CT in brain tumors: impact on multidisciplinary brain tumor board decisions.

Jérôme Barriere was inadvertently missing in the original version of this article. He has participated to the study design, protocol writing and inclusion of a significant number of patients.

18F-DOPA PET/CT in brain tumors: impact on multidisciplinary brain tumor board decisions.

PURPOSE: This study aimed to assess the therapeutic impact and diagnostic accuracy of 18F-DOPA PET/CT in patients with glioblastoma or brain metastases. METHODS: Patients with histologically proven glioblastoma or brain metastases were prospectively included in this monocentric clinical trial (IMOTEP). Patients were included either due to a clinical suspicion of relapse or to assess residual tumor infiltration after treatment. Multimodality brain MRI and 18F-DOPA PET were performed. Patients' data were discussed during a Multidisciplinary Neuro-oncology Tumor Board (MNTB) meeting. The discussion was first based on clinical and MRI data, and an initial diagnosis and treatment plan were proposed. Secondly, a new discussion was conducted based on the overall imaging results, including 18F-DOPA PET. A second diagnosis and therapeutic plan were proposed. A retrospective and definitive diagnosis was obtained after a 3-month follow-up and considered as the reference standard. RESULTS: One hundred six cases were prospectively investigated by the MNTB. All patients with brain metastases (N = 41) had a clinical suspicion of recurrence. The addition of 18F-DOPA PET data changed the diagnosis and treatment plan in 39.0% and 17.1% of patients' cases, respectively. Concerning patients with a suspicion of recurrent glioblastoma (N = 12), the implementation of 18F-DOPA PET changed the diagnosis and treatment plan in 33.3% of cases. In patients evaluated to assess residual glioblastoma infiltration after treatment (N = 53), 18F-DOPA PET data had a lower impact with only 5.7% (3/53) of diagnostic changes and 3.8% (2/53) of therapeutic plan changes. The definitive reference diagnosis was available in 98/106 patients. For patients with tumor recurrence suspicion, the adjunction of 18F-DOPA PET increased the Younden's index from 0.44 to 0.53 in brain metastases and from 0.2 to 1.0 in glioblastoma, reflecting an increase in diagnostic accuracy. CONCLUSION: 18F-DOPA PET has a significant impact on the management of patients with a suspicion of brain tumor recurrence, either glioblastoma or brain metastases, but a low impact when used to evaluate the residual glioblastoma infiltration after a first-line radio-chemotherapy or second-line bevacizumab.

The Pathophysiology of Watershed Infarction: A Three-Dimensional Time-of-Flight Magnetic Resonance Angiography Study.

BACKGROUND: Most of the time, watershed infarcts (WIs) involve steno-occlusive carotid disease. The pathophysiological mechanism could be predicted by their pattern: internal WIs (IWIs) are thought to be due to hemodynamic impairment in contrast to cortical WIs (CWIs), which are more likely to be caused by microembolic phenomena. We used a 3D time-of-flight (TOF) magnetic resonance angiography (MRA) study to assess this hypothesis. METHODS: In 45 consecutive patients with a recent WI and ipsilateral cervical carotid stenosis, clinical and radiological data were obtained retrospectively. 3D TOF MRA were analyzed both qualitatively and quantitatively (internal carotid and anterior, middle and posterior cerebral arteries). Then, 2 groups were determined depending on their radiological patterns: WIs with (IWI+) or without (IWI-) an internal watershed. RESULTS: Thirty-two of the 45 patients (71%) had IWIs that were or were not associated with CWIs (IWI+), while 13 patients (29%) had only CWIs (IWI-). There was no significant relationship between the radiological pattern and the demographic data, the cardiovascular risk factors, or the degree of stenosis. However, IWI+ patients more frequently had motor weakness (P = .03) than CWI patients. An ipsilateral reduced middle cerebral artery intensity on 3D TOF MRA in both qualitative and quantitative analyses was significantly associated with IWI+. Instead within IWI-, no significantly reduced signal intensity was found. CONCLUSION: These findings originally support the view that IWIs are mainly caused by a hemodynamic impairment related to carotid stenosis, whereas CWIs are mostly due to a microembolic mechanism. 3D TOF MRA, which gives pertinent information on pathophysiology on IWIs, can help in decision making.

Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes.

PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). METHODS: We identified 101 patients with inconclusive findings who underwent an [(123)I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. RESULTS: Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. CONCLUSION: The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [(123)I]FP-CIT SPECT in PS patients with previously inconclusive findings. The gain in accuracy might be achieved by better discrimination between physiological low striatal [(123)I]FP-CIT binding due to age-related loss of the dopamine transporter or pathological loss of binding.

Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls.

PURPOSE: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. RESULTS: Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123)I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors.

Review of the PRIODAC project on thyroid protection from radioactive iodine by repeated iodine intake in individuals aged 12.

BACKGROUND: Intake of potassium iodide (KI) reduces the accumulation of radioactive iodine in the thyroid gland in the event of possible contamination by radioactive iodine released from a nuclear facility. The WHO has stated the need for research for optimal timing, appropriate dosing regimen and safety for repetitive iodine thyroid blocking (ITB). The French PRIODAC project, addressed all these issues, involving prolonged or repeated releases of radioactive iodine. Preclinical studies established an effective dose through pharmacokinetic modeling, demonstrating the safety of repetitive KI treatment without toxicity. SUMMARY: Recent preclinical studies have determined an optimal effective dose for repetitive administration, associated with pharmacokinetic modelling. The results show the safety and absence of toxicity of repetitive treatment with KI. Good laboratory practice level preclinical studies corresponding to individuals > 12 years have shown a safety margin established between animal doses without toxic effect. After approval from the French health authorities, the market authorization of the 2 tablets of KI-65mg/day was defined with a new dosing scheme of a daily repetitive intake of the treatment up to 7 days unless otherwise instructed by the competent authorities for all categories of population except pregnant women, and children under the age of 12 years. CONCLUSIONS: This new marketed authorization resulting from scientific-based evidence obtained as part of the PRIODAC project may serve as an example to further harmonize the application of KI for repetitive ITB in situations of prolonged radioactive release at the European and International levels, under the umbrella of the WHO.

Automatic semi-quantification of [123I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2: results from the ENC-DAT database.

PURPOSE: The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects. METHODS: The study included 122 healthy subjects, aged 18-83 years, recruited in the multicentre 'ENC-DAT' study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [(123)I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the 'BasGan' software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables. RESULTS: SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p < 0.0001) and gender (women had higher values; p = 0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p < 0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p < 0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects. CONCLUSION: This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.

[18F]-FDopa positron emission tomography imaging in corticobasal syndrome.

PURPOSE: First, to investigate the patterns of [18F]-FDOPA positron emission tomography imaging in corticobasal syndrome using visual and semi-quantitative analysis and to compare them with patterns found in Parkinson's disease and progressive supranuclear palsy. Then, to search for correlations with clinical features and [18F]-FDG positron emission tomography imaging. METHODS: 27 corticobasal syndrome patients who underwent [18F]-FDOPA positron emission tomography imaging were retrospectively studied. They were compared to 27 matched Parkinson's disease patients, 12 progressive supranuclear palsy patients and 53 normal controls. Scans were visually assigned to one of the following patterns: normal; unilateral homogeneous striatal uptake reduction; putamen uptake reduction with putamen-caudate gradient. A semi-quantitative analysis of striatal regional uptake and asymmetry was performed and correlated to clinical features and [18F]-FDG positron emission tomography patterns. RESULTS: [18F]-FDOPA positron emission tomography appeared visually abnormal in only 33.5% of corticobasal syndrome patients. However, semi-quantitative analysis found putaminal asymmetry in 63%. Striatal uptake was homogeneously reduced in both putamen and caudate nucleus in corticobasal syndrome patients unlike in Parkinson's disease and progressive supranuclear palsy. No correlation was found between [18F]-FDOPA positron emission tomography and clinical features. Half of corticobasal syndrome patients presented a corticobasal degeneration pattern on [18F]-FDG positron emission tomography.  CONCLUSION: [18F]-FDOPA positron emission tomography can often be normal in corticobasal syndrome patients. Semi-quantitative analysis is useful to unmask a significant asymmetry in many of them. Homogeneous striatal uptake reduction contralateral to the clinical signs is highly suggestive of corticobasal syndrome. This finding can be helpful to better characterize this syndrome with respect to Parkinson's disease and progressive supranuclear palsy.

PET Imaging in Neuro-Oncology: An Update and Overview of a Rapidly Growing Area.

PET plays an increasingly important role in the management of brain tumors. This review outlines currently available PET radiotracers and their respective indications. It specifically focuses on 18F-FDG, amino acid and somatostatin receptor radiotracers, for imaging gliomas, meningiomas, primary central nervous system lymphomas as well as brain metastases. Recent advances in radiopharmaceuticals, image analyses and translational applications to therapy are also discussed. The objective of this review is to provide a comprehensive overview of PET imaging's potential in neuro-oncology as an adjunct to brain MRI for all medical professionals implicated in brain tumor diagnosis and care.

EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2.

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using (123)I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the "Kompetenznetz-Parkinson" sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2.

The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice.The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with (123)I [1] and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines intend to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.

Comparison of 3 γ-probes for simultaneous iodine-125-seed and technetium-99m breast cancer surgery: NEMA standard characterisation with extended processing.

PURPOSE: Iodine-125 (125I) seeds can be used as landmarks to locate non-palpable breast lesions instead of implanting metal wires. This relatively new technique requires a nuclear probe usually used for technetium-99m (99mTc) sentinel node detection. This study aimed to compare the performances of different probes and valid the feasibility of this technique, especially in the case of simultaneous 125I-seed and 99mTc breast cancer surgery. METHODS: Three probes with different features (SOE-3211, SOE-3214 and GammaSUP-II) were characterised according to the NEMA NU3-2004 standards for a 99mTc source and a 125I-seed. Several tests such as sensitivity, linearity or spatial resolution allowed an objective comparison of their performances. NEMA testing was extended to work on signals discrimination in case of simultaneous detection of two different sources (innovative figure of merit "Shift Index") and to assess the 99mTc scatter fraction, a useful parameter for the improvement of the probes in terms of detector materials and electronic system. RESULTS: Although the GammaSUP-II probe saturated at a lower activity (1.6 MBq at 10 mm depth), it allowed better sensitivity and spatial resolution at the different NEMA tests performed with the 99mTc source (7865 cps/MBq and 15 mm FWHM at 10 mm depth). With the 125I-seed, the GammaSUP-II was the most sensitive probe (3106 cps/MBq at 10 mm depth) and the SOE-3211 probe had the best spatial resolution (FWHM 20 mm at 10 mm depth). The SOE-3214 probe was more efficient on discriminating 125I from 99mTc in case of simultaneous detection. The SOE probes were more efficient concerning 99mTc scatter fraction assessments. The SOE-3211 probe, with overall polyvalent performances, seemed to be an interesting trade-off for detection of both 125I and 99mTc. CONCLUSION: The three probes showed heterogeneous performances but were all suitable for simultaneous 99mTc sentinel node and 125I-seed detection. This study provides an objective and innovative methodology to compare probes performances and then choose the best trade-off regarding their expected use.

Baseline metabolic tumor volume as a strong predictive and prognostic biomarker in patients with non-small cell lung cancer treated with PD1 inhibitors: a prospective study.

BACKGROUND: Reliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors. METHODS: Maximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD). RESULTS: A high MTV and a high TLG were significantly associated with a lower OS (p<0.001). The median OS in patients with MTV above the median (36.5 cm3) was 10.5 months (95% CI: 6.2 to upper limit: unreached), while the median OS in patients with MTV below the median was not reached. Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI: 0.65 to 0.87 and 0.72, 95% CI: 0.62 to 0.84, respectively). CONCLUSION: MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.

Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice.

SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone ß-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.