Valeur pronostique de la TEP/TDM dans le bilan initial du cancer du col utérin : SUVmax de la tumeur primitive et stadification ganglionnaire

PurposeWe investigated the prognostic significance of F-18 fluorodeoxyglucose (FDG) uptake measured as maximum Standardized Uptake Value (SUV_max) in primary tumor by positron emission tomography/computed tomography (PET/CT) in cervical cancer. The secondary objective was to determine the accuracy of the PET/CT for detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastases.MethodsThis retrospective study included 49 consecutive patients with stage IB1 to IVB cervical cancer. Univariate analysis was performed to determine the relationships between SUV_max value and pathological prognostics factors. Survival was estimated by Kaplan-Meier method. The gold standard of LN metastases was histologic.ResultsA significant difference in SUV_max was observed between stage I and stage II, stage I and stage IV and tumor size ≤ 4 cm and > 4 cm (P = 0.0001). There was a significant correlation between the SUV_max and tumor maximal size (r = 0.597) (P < 0.0001). PLN metastasis was found to be predictive of progression-free survival (P = 0.0007). The negative predictive value (NPV) of the PET/CT for PALN was 100% for locally advanced cervical carcinoma in 24 patients. The specificity and NPV of the PET/CT for PLN in eight early-stage cervical cancer were 100% and 87.5% (7/8) respectively. The PET/CT false-negative PLN measured less than 2 mm.ConclusionOur results demonstrate a correlation between SUV_max and tumor maximal size, which represents an indicator of tumor aggressiveness. PET/CT is effective to predict the absence of PALN in locally advanced cervical carcinoma. PET/CT is not sufficient to predict PLN in early-stage cancer without lymphadenectomy.     

Use of choline tracers in the prostate carcinoma management

Prostate cancer is the second most frequently diagnosed cancer in men. This incidence has increased because of the introduction of screening with prostate-specific antigen (PSA) and the use of improved biopsy techniques. Choline PET/CT cannot be recommended as a first-line screening procedure for primary prostate cancer. PET/CT has a limited sensitivity due to its dependency on tumor configuration and size, and a limited specificity in differentiation between prostate cancer and benign pathologies. PET/CT could be useful in the detection of malignant lymph nodes in case of nodes greater than 5 mm in diameter. An application of choline PET/CT may be to increase the detection rate of clinically suspected prostate cancer with multiple negative prostate biopsies. Choline PET/CT has proved to be useful for restaging patients with prostate cancer with biochemical failure. Studies have shown that the positive detection rate of choline PET/CT increases with increasing PSA values. The definition of a PSA cut-off value to refer prostate carcinoma with biochemical recurrence would be helpful for the clinical management of these patients. Several PSA cut-off values have been proposed by literature. The routine use of choline PET/CT cannot be recommended only in patients with an absolute PSA value of < 1 ng/mL. Moreover, the sensitivity of ¹⁸F-Fluorocholine (FCH) PET/CT is significantly higher in patients with a PSA velocity > 2 ng/mL per year or a PSA-doubling time ≤ 6 months. In case of early bone metastases ¹⁸F-FCH could be superior to ¹⁸F-sodium fluoride due to the absence of bone reaction and remodelling.     

Quantification and monitoring of PET/CT data in multicentre trials: The Swiss SAKK 56/07 trial experience

AimTo outline the importance of continuous monitoring of quantitative positron emission tomography (PET) data in multicentre trials to minimize quantitative bias in longitudinal intra-patient PET studies in light of the multicentre SAKK 56/07 experience in quantification and monitoring ¹⁸F-FDG PET/CT data.Patients and methodsWe collected 64 uniform phantom ¹⁸F-FDG PET acquisitions periodically at the enrolling centres (12 European institutions). A core-laboratory analysed them for standard uptake value (SUV) accuracy (desired 1.00 ± 10%) and acceptable image noise was defined by a coefficient of variation (COV) less than 15%. In total, 151 patients ¹⁸F-FDG PET acquisitions (baseline and follow-up) were also collected and analysed to verify longitudinal coherence of main acquisition/reconstruction parameters (DICOM tags verification) and patient preparation, in particular the uptake time (desired uptake time [UT] = 60 ± 10 min).ResultsUniform phantom PET acquisition satisfied the inclusion criteria in 58/64 (89%) examinations. All PET scanner exhibited comparable SUV quantification, but we found large dispersion in terms of noise, with COV ranging 3–15%. Only 1 phantom PET acquisition was out of range with COV = 21.5%. Patient data exhibited important variation in uptake time with UT = 65 ± 10 min (mean ± SD), with only 111/151 (74%) patients’ examinations satisfying inclusion criteria while 26% were out of range.ConclusionsRegular monitoring of PET data in multicentre trials is capital to ensure longitudinal intra-patient PET data consistence and minimize quantitative bias while it helps to spread the culture of quality in participating centre. Recent EARL (EANM Research Ltd) standardization and unification of procedures is a welcome step in this direction.     

Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

PurposeTo investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model.MethodsPBPK parameters were estimated using biokinetic data of 15 patients after injection of (152 ± 15) MBq of ¹¹¹In-DTPAOC (total peptide amount (5.78 ± 0.25) nmol). True mathematical phantoms of patients (MPPs) were the PBPK model with the estimated parameters. Dynamic PET measurements were simulated as being done after bolus injection of 150 MBq ⁶⁸Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35 min p.i. (P₁), 4 h p.i. (P₂) and the combination of P₁ and P₂ (P₃) were simulated. Each measurement was simulated with four frames of 5 min each and 2 bed positions. PBPK parameters were fitted to the PET data to derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of 5.1 GBq of ⁹⁰Y-DOTATATE over 30 min in both true and PET-predicted MPPs. TIACs of simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs (predicted TIACs) followed by the calculation of variabilities v.ResultsFor P₁ and P₂ the population variabilities of kidneys, liver and spleen were acceptable (v < 10%). For the tumours and the remainders, the values were large (up to 25%). For P₃, population variabilities for all organs including the remainder further improved, except that of the tumour (v > 10%).ConclusionTreatment planning of PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen using a PBPK model and patient specific information.     

TEP au 18-FDG et carcinose péritonéale d’origine ovarienne : valeurs diagnostique et pronostique avant chimio-hyperthermie intra-péritonéale (CHIP)

AimEvaluate 18-FDG PET/CT diagnostic and prognostic value before HIPEC.Materials and methodsThis retrospective monocentric study included 38 patients with recurrent (n = 27) or primary (n = 11) ovarian cancer who were blinded reviewed for the presence of peritoneal lesions on PET/CT before HIPEC treatment. The results were compared to surgical and histopathological findings, and to survival curves.ResultsThirty-two patients had peritoneal carcinomatosis based on surgical and histopathological findings, and 19 based on PET. There was no suspicious site of abnormal FGD uptake in the supradiaphragmatic regions. The sensitivity and specificity were respectively 56.2 and 100%. Among the 14 false negative patients, 11 had infracentimetric peritoneal implants, and most of them (n = 13) had chemotherapy before HIPEC. There was significantly more patients treated by chemotherapy in the negative PET group (P = 0.02). Even if the event rate observed was higher in the positive PET group for both event free and overall survival (respectively 68% vs. 64% and 26.3% vs. 17.6%), no significant difference was observed using the survival curves (respectively P = 0.62 and 0.59).ConclusionFDG PET/CT before HIPEC showed excellent specificity and lower sensitivity, due to small peritoneal implants and probably to chemotherapy before HIPEC. No significant prognostic value of FDG PET was observed in our study. FDG PET could be considered as a useful tool for detecting distant metastasis with an impact on therapeutic management.     

Confrontation des données de la TEP/TDM au 18FDG initiale aux statuts p16 (INK4a) et HPV des cancers des VADS localement avancés traités par radiochimiothérapie

PurposeThe overexpression of p16 and HPV status are now well established as independent prognostic factors in head and neck squamous cell carcinoma (HNSCC). It was suggested that some parameters derived from initial 18F-FDG PET are also independent prognostic factors. Our purpose was to study the correlation between virology and pretreatment PET/CT in locally advanced HNSCC treated by radio-chemotherapy.MethodsForty HNSCC patients with tumor volumes > 3 cm³ were prospectively recruited. All patients underwent initial 18F-FDG PET/CT, from which metabolic volume, intensity (SUV), overall activity, heterogeneity and shape parameters were extracted. The correlation of these parameters with virological data extracted from pre treatment biopsy, including p16 expression, DNA HPV 16 and HPV status (p16 + DNA HPV 16) was subsequently studied.ResultsP16 + tumors exhibited higher SUV_max (P = 0.028) and SUV_mean (P = 0.02). P16+ tumors were also more heterogeneous, albeit with a lower correlation (P = 0.004 for local heterogeneity). In addition, P16+ and HPV+ tumors were characterized by less complex shapes (P = 0.03).ConclusionLocally advanced HNSCC show specific PET characteristics in case of P16+ tumors. The relationship between those different biological characterization approaches and overall patient outcome needs to be investigated.     

TEP/TDM 18F-choline dans les récidives biologiques des cancers de la prostate traites par radiothérapie externe ou curiethérapie : impact du PSA et de sa cinétique

AimTo determine the impact of PSA and its kinetics on ¹⁸F-Choline PET/CT (FCH PET) ability to detect site of relapse in prostate cancer initially treated with external beam radiotherapy (EBRT) or brachytherapy (IBT).MethodsWe retrospectively enrolled PET FCH performed for suspicion of biochemical relapse after EBRT/IBT from January 2010 to January 2017 at Institut Curie. PSA_trigger, ΔPSA_nadir (PSA_trigger-PSA_nadir), PSA doubling time (PSA_dt) and velocity (PSA_vel) were compared between positive and negative results. Logistic regression analysis was used to determine the relationship between these parameters and PET ability to detect True Positives (TP).ResultsIn all, 271 FCH PET met the inclusion criteria: 169 after treatment with EBRT and 102 after IBT. Positivity rate was 67.9%, and 63.4% of TP were local relapses. Overall sensitivity and specificity were 81.2% and 71.0%. PSA_trigger was 3.32 ng/mL (interquartile space: IQS 2.28–5.77) when PET was negative and 5.15 ng/mL (IQS 3.16–10.17) when positive, ΔPSAnadir was respectively 2.76 ng/mL (IQS 1.84–4.69) and 4.57 ng/mL (IQS 2.48–8.85), PSA_dt 10.78 months (IQS 5.46–20.07) and 7.23 months (EI 2.58–14.14), and PSA_vel 2.16 ng/mL/year (EI 1.02–4.80) et 4.92 ng/mL/year (1.89–16.02) (P < 0.001). Positivity rate increased with PSA_trigger and ΔPSA_nadir. We found PSA_dt ≤ 9 months (P = 0.029; OR = 2.97, IC_95% [1.12–7.88]) and ΔPSA_nadir ≥ 3 ng/mL (P = 0.03; OR = 2.56, IC_95% [1.37–4.77]) to be independent predictive factors of PET sensitivity.ConclusionDetection of relapse after EBRT or IBT with PET FCH is influenced by PSA and its kinetics. In our study, PSA_dt and ΔPSA_nadir were independant predictors of PET performance, but initial treatment and tumor characteristics were not.     

Comparison of 68GA-FAPI-04 PET/CT and 18F-FDG PET/CT in detection of metastatic bone disease in various cancers

ObjectiveOur aim in this retrospective study was to compare the diagnostic accuracy of ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT in detecting bone metastases of various cancers and to evaluate the potential usefulness of ⁶⁸Ga-FAPI-04 PET/CT in detecting metastatic bone disease.Material and methodOur retrospective study included 44 patients diagnosed with bone metastases due to various cancers between January 2021 and February 2022. All patients underwent ⁶⁸Ga-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT imaging within 14 days. In the semi-quantitative analysis of the skeletal system, all regions with higher uptake than background activity were considered pathological. SUVmax and Metastasis-to-background ratio (TBR) values were calculated from metastatic sites.ResultsA total of 827 bone metastases were detected in our study. The diagnostic accuracies of FAPI PET/CT and ¹⁸F-FDG PET/CT were 91.8% and 81.5%, respectively (P < 0.001). When all bone metastases were compared, the SUVmax of ⁶⁸Ga-FAPI-04 PET/CT was statistically significantly higher than that of ¹⁸F-FDG PET/CT (median 6.15 vs. 5.2; P < 0.001). When FDG and FAPI SUVmax values were compared according to metastasis types, FAPI SUVmax and TBR values in osteolytic, medullary and mixed type bone metastases were found to be statistically significantly higher than FDG (P-values: < 0.001, < 0.001, < 0.001, respectively). There was no statistically significant difference between FDG and FAPI SUVmax values in osteoblastic bone metastases (P = 0.26).ConclusionIt has been shown that ⁶⁸Ga-FAPI-04 PET/CT is superior to ¹⁸F-FDG PET/CT in detecting metastatic bone disease and may have more clinical impact on disease management.     

A simple noninvasive index to predict significant liver fibrosis in patients with advanced schistosomiasis japonica

BackgroundSchistosoma japonicum causes marked liver fibrosis, while lethal syndromes present in advanced schistosomiasis patients. Its management depends on the degree of fibrosis present.Patients and methodsFifty-two patients were recruited to assess the diagnostic value of bio-markers in patients with advanced schistosomiasis japonica. Fibrosis was assessed in liver biopsies using METAVIR system. The correlation between conventional parameters and significant fibrosis (F2-F4) was assessed using univariate analysis and logistic regression. The method of area under receiver operating characteristic curves (AUROCs) was used as a measurement of diagnostic efficacy.ResultsWhite blood cell counts, platelet counts and albumin (all P < 0.05) were significantly lower, while prothrombin time, international normalized ratio (INR), hyaluronic acid (HA), IV collagen and ultrasound fibrosis scores (all P < 0.01) were significantly elevated in F2-F4 patients compared with F0-F1 patients. HA and INR were identified as independent predictors by multivariate analysis (P = 0.023 and P = 0.013, respectively). Of the routine laboratory tests for the diagnosis of significant fibrosis, HA gave the best AUROC of 0.875 (95% confidence interval (CI): 0.701–0.997). We constructed a new simple index (INR × HA/100) to discriminate between F2-F4 patients and F0-F1 patients. It showed the highest AUROC of 0.921 (95% CI: 0.828-1.000), and had better diagnostic values than APRI and FIB-4.ConclusionHA and INR were reliable markers for differentiating significant liver fibrosis in patients with advanced schistosomiasis japonica. And the new simple index can easily predict significant liver fibrosis with a high degree of accuracy.     

Segmentation d’images de lésions cérébrales primitives en TEP FET : influence du volume de travail

Purpose(1) Evaluate the reproducibility of segmentation methods depending on the preselection region for tumour volume determination on ¹⁸F-fluoro-ethyl-tyrosine (FET) PET. (2) Evaluate the intra and inter-operator reproducibility of the manual delineation. (3) Compare this delineation with the segmentation methods.Materials and methodsEighteen FET PET of patients with glioblastoma were analysed. Preselection regions were determined prior to any segmentation. Two physicians delineated the tumour volume manually. The tumour volume was also delineated with a threshold method (40 and 70% of SUV_max), and a random walk based method. Pearson coefficient (r) (P < 0.05 for r > 0.468) and Jaccard indices (JI) were used to compare the volumes.ResultsManual delineation was reproducible with r = 0.97 and IJ = 0.65 for intra-operator, and r = 0.76 and IJ = 0.45 for inter-operator reproducibility. The preselection regions for a given lesion were different and the segmentation varied with the preselection region: r = 0.55 JI = 0.58; r = 0.85 JI = 0.83; r = 0.70 JI = 0.39 respectively for the threshold of 40%, 70% and the random walk. The segmentation differed form de manual delineation with r = 0.37 and JI = 0.16; r = 0.54 and JI = 0.42; r = 0.43 and JI = 0.37 respectively for the threshold of 40%, 70% and the random walk.ConclusionThe reproducibility of the segmentation methods depends extensively on the preselection region. The intra-operator reproducibility of cerebral lesion delineation on FET PET is satisfactory. The inter-operator reproducibility could be improved.     

Differential diagnosis between progression and radionecrosis in brain metastases after stereotactic radiosurgery using hybrid FDG-PET and MRI coregistered images

IntroductionDual phase 18 FDG brain PET is helpful to assess brain metastases (BM) as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory processes. This is useful when MRI can’t discriminate brain tumor recurrence (TR) rom radionecrosis (RN) after stereotaxic radiosurgery (SRS) for BM. Many studies have sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many biases, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers.Materials and methodsWe retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET consisted in an “early” and “delayed” acquisition, respectively 30 minutes and 4 h after injection. MRI included permeability and perfusion sequences. PET and MRI data were all coregistered on the contrast enhanced T1 MRI images. Semi-automated Volumes of Interest (VOI) of the tumor were drawn on the BM and a reference contralateral white-matter ROI (WM) was drawn for standardization; every metric was calculated inside these ROIs, in particular the tumor SUVmax and its variation in time. A 20% increase in the tumor SUVmax was in favor of TR while a modification of less than 100% was in favor of RN. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up.ResultsNine patients were ruled out as TR and 6 as RN. After standardization, there was a significant difference between groups for VP (P = 0.042), Washin (P = 0.035), Peak Enhancement (P = 0.037), standardized delayed SUVmax (P = 0.008) and RI (P = 0.016). Semi-quantitative analysis found respectively for PET and MRI a Sensitivity of 100% and 87.5% and a Specificity of 100% and 85.71%.ConclusionCoregistered PET-MRI images accurately discriminate between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.     

Intérêt pronostique et prédictif de la TEP-TDM au 18F-FDG au bilan initial des mélanomes de stade IIIB-C-D et IV avant traitement par anti-PD-1

PurposeThe advent of immunotherapy by checkpoint inhibitor has profoundly changed the prognosis of patients with metastatic melanoma. The objective of our study was to evaluate the prognostic and predictive performance of 18F-FDG PET/CT of the initial extension assessment of stage IIIB-C-D and IV melanomas.MethodsWe retrospectively included 57 patients who had 18F-FDG PET/CT prior to the introduction of anti-PD-1 immunotherapy. The parameters extracted were SUVmax, SUV peak, MTV and TLG of the lesion with highest uptake (MTV LM, TLG LM), as well as MTV total and TLG total, obtained by adaptive segmentation. The18F-FDG PET/CT were dichotomized using the optimal threshold measured according to the area under the curve in the ROC (Receiver Operation Characteristic) curves. These parameters were evaluated using a Cox model. Overall survival and progression-free survival analyses were performed using the Kaplan Meier model.ResultsThe median follow-up was 25.4 months, 38 patients had progressed or recurred, and 20 patients had died. TLG LM > 132.59 (P = 0.0011), MTV total > 12 cm³ (P = 0.0139), and TLG > 94.17 (P = 0.0084) were significantly associated with a shorter progression-free survival. TLG LM > 145.92 (P = 0.0062), MTV total > 10.16 cm³ (P = 0.0051), and a metastatic spread > 2 organs (P = 0.0001) were associated with a shorter overall survival.ConclusionWe confirm the potential prognostic interest of PET-TDM at 18FDG before immunotherapy of stage IIIB-C-D and IV melanomas on progression-free survival and overall survival. The combination of these metabolic markers reflecting tumor burden with clinical and biological prognostic factors could allow early identification of patients at high risk of anti-PD-1 failure.     

Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists

Movement disorders such as Parkinson’s disease and Huntington’s disease are serious life-limiting and debilitating movement disorders. Their onset typically occurs from mid-life to late in life, and effective diagnostic techniques for detecting and following the disease course are lacking. Our goal is to develop receptor imaging agents for positron emission tomography (PET) that selectively target the most relevant subtype of adenosine receptors (AR) that are highly expressed in the striatum, that is, the A_2A AR. To further this goal, we have synthesized and characterized pharmacologically a family of high affinity A_2A AR ligands, based on the known antagonist, SCH 442416 (R = –Me), which have structural variability on the terminus (R = –Et, –i-Pr, –allyl, and others). A O-fluoroethyl analogue suitable for use as a PET tracer had a K_i value of 12.4 nM and was highly selective for the A_2A AR in comparison to the A₁ and A₃ ARs.     

A novel biotransformation of astragalosides to astragaloside IV with the deacetylation of fungal endophyte Penicillium canescens

Under the deacetylation of fungal endophyte Penicillium canescens, which was isolated from pigeon pea, a novel and highly efficient biotransformation method of astragalosides to astragaloside IV in Radix Astragali was investigated. After single factor tests of the biotransformation procedure, the optimum biotransformation conditions were confirmed as the liquid solid ratio 20:1, the biotransformation temperature 30 °C, time 36 h and pH 7, respectively. Final content of astragaloside IV in Radix Astragali reached 7.66 ± 0.44 mg/g, which was 5.51-fold to that of untreated one and contents of astragaloside I and astragaloside II significantly decreased. The immobilized Ca-alginate gel beads with P. canescens could be reused at least for 13 runs. This is the first report that fungal endophyte was applied for the biotransformation of astragalosides to astragaloside IV in Radix Astragali and this novel high-efficiency biotransformation method will be an alternative to enhance the content of astragaloside IV in Radix Astragali in commercial process.     

A novel side-bridged hybrid phosphonate/acetate pendant cyclam: Synthesis,characterization, and 64Cu small animal PET imaging

Copper-64 (t_1/2 = 12.7 h; β⁺: 0.653 MeV, 17.4%; β^?: 0.578 MeV, 39%) is produced in a biomedical cyclotron and has applications in both imaging and therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind copper radionuclides to antibodies and peptides owing to their relatively high kinetic stability. A novel side-bridged cyclam featuring both pendant acetate and phosphonate groups was synthesized using a Kabachnik–Fields approach followed by hydrobromic acid deprotection. The Cu(II) complex of the novel ligand was synthesized, radiolabeling with ⁶⁴Cu was demonstrated, and in vitro (serum) stability was performed. In addition, in vivo distribution and clearance of the ⁶⁴Cu-labeled complex was visualized by positron emission tomography (PET) imaging. This novel chelate may be useful in ⁶⁴Cu-mediated diagnostic positron emission tomography (PET) imaging as well as targeted radiotherapeutic applications.     

Simultaneous quantification of rosiglitazone and its two major metabolites,N-desmethyl and p-hydroxy rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry: Application to a pharmacokinetic study

We present a simple, rapid, and sensitive liquid chromatography (LC)–tandem mass spectrometry (MS/MS) method for the simultaneous quantification of rosiglitazone and its two major metabolites via CYP2C8/9, N-desmethyl and p-hydroxy rosiglitazone, in human plasma. The procedure was developed and validated using rosiglitazone-d₃ as the internal standard. Plasma samples (0.1 ml) were prepared using a simple deproteinization procedure with 0.2 ml of acetonitrile containing 40 ng/ml of rosiglitazone-d₃. Chromatographic separation was carried out on a Luna C₁₈ column (100 mm × 2.0 mm, 3-μm particle size) using an isocratic mobile phase consisting of a 60:40 (v/v) mixture of acetonitrile and 0.1% formic acid_(aq). Each sample was run at 0.2 ml/min for a total run time of 2.5 min per sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization at m/z 358.1 → 135.1 for rosiglitazone, m/z 344.2 → 121.1 for N-desmethyl rosiglitazone, m/z 374.1 → 151.1 for p-hydroxy rosiglitazone, and m/z 361.1 → 138.1 for rosiglitazone-d₃. The linear ranges of concentration for rosiglitazone, N-desmethyl rosiglitazone, and p-hydroxy rosiglitazone were 1–500, 1–150, and 1–25 ng/ml, respectively, with a lower limit of quantification of 1 ng/ml for all analytes. The coefficient of variation for assay precision was less than 14.4%, and the accuracy was 93.3–112.3%. No relevant cross-talk and matrix effect were observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 4-mg rosiglitazone tablet to healthy male Korean volunteers.     

Intérêt de la tomographie par émission de positons (TEP) au 18FDG dans le suivi des patients traités pour carcinome épidermoïde des voies aérodigestives supérieures (VADS) en rémission clinique

IntroductionPosttreatment follow-up of head and neck squamous cell carcinoma (HNSCC) recurrence is a diagnostic challenge. Tissue distortions from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination (PE), computed tomography, and magnetic resonance imaging. A number of studies have shown that ¹⁸Fluoro-fluorodeoxyglucose (¹⁸FDG) Positron emission tomography (PET) may be an effective technique for the detection of persistent, recurrent, and distant metastatic HNSCC after treatment. The aim of this prospective study was to determine the benefits (sensitivity, specificity, predictive values, and accuracy) of ¹⁸FDG PET using hybrid PET–Computed tomography system (PET/CT) in the detection of HNSCC subclinical locoregional recurrence and distant metastases, in patients 12 months after curative treatment with a negative conventional follow up.Materials and MethodsNinety-one patients cured from head and neck squamous cell carcinoma (HNSCC) without any clinical element for recurrence were included. Whole-body ¹⁸FDG PET/CT examination was performed 11.6 ± 4.4 months after the end of the treatment. The gold standard was histopathology or 6 months imaging follow-up.ResultsThe whole-body ¹⁸FDG PET/CT of the 91 patients in this study consisted of 52 negative and 39 positive results. Nine of these patients who exhibited abnormal ¹⁸FDG uptake in head and neck area did not have subsequently proven recurrent HNSCC (false positive). Thirty had proven recurrence (true positive). All 52 patients with negative readings of ¹⁸FDG PET/CT remained free of disease at 6 months (true negative). The sensitivity and specificity of ¹⁸FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100% (30/30) and 85% (52/61) respectively. The positive predictive value was 77% (30/39). The negative predictive value was 100% (52/52). The overall accuracy was 90% (82/91).ConclusionThe results of our study confirm the high effectiveness of ¹⁸FDG PET/CT in assessment of HNSCC recurrence. It suggests that this modality is more accurate than conventional follow-up PE alone in the assessment of patient recurrence after previous curative treatment for HNSCC. Therefore, a PET study could be systematically proposed at 12 months after the end of the treatment.     

Performances de la TEP au 18F-FDG dans la caractérisation initiale de la lésion primitive du cancer du sein

Objective¹⁸F-FDG PET/CT is for the moment not recommended for stage T of the TNM classification of breast cancer. The aim of our study was to evaluate the performance of ¹⁸F-FDG PET/CT in the initial staging of breast tumors. Tumor size, skin involvement and inflammation as well as the relationship between primary tumor maximum standardized uptake value (SUVmax) and histopathological grade (SBR), molecular tumor subtypes (luminal A and B, Her2 enriched, triple negative), estrogen receptors (ER), progesterone receptors (PR) and focality were evaluated.MethodsHistological reports of patients operated for breast cancer, without neoadjuvant chemotherapy, were compared to preoperative ¹⁸F-FDG PET/CT.ResultsSeventy-four patients who underwent surgery in 2016 were included. ¹⁸F-FDG PET/CT was able to visualize primary tumors in 91% and to correctly classify the T stage of the TNM classification in 81% of the cases, to detect multifocality in 73% and cutaneous and inflammatory breast cancers in 100%. The uptake intensity of ¹⁸F-FDG (SUVmax) was significantly correlated with histo-prognostic factors such as SBR grade (P = 0.02), lack of expression of estrogen receptors (ER) (P = 0.01) and progesterone (PR) (P = 0.02), positive HER2 status (P = 0.01) or triple negative subtype tumors (P = 0.02).Conclusion¹⁸F-FDG PET/CT provides relevant elements for local assessment, in particular, tumor focality and inflammatory character in addition to ensuring the regional and extension assessment.     

Synthesis and in vivo evaluation of [18F]2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione ([18F]FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates

The 5-HT_1AR partial agonist PET radiotracer, [¹¹C]CUMI-101, has advantages over an antagonist radiotracer as it binds preferentially to the high affinity state of the receptor and thereby provides more functionally meaningful information. The major drawback of C-11 tracers is the lack of cyclotron facility in many health care centers thereby limiting widespread clinical or research use. We identified the fluoroethyl derivative, 2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (FECUMI-101) (K_i = 0.1 nM; E_max = 77%; EC₅₀ = 0.65 nM) as a partial agonist 5-HT_1AR ligand of the parent ligand CUMI-101. FECUMI-101 is radiolabeled with F-18 by O-fluoroethylation of the corresponding desmethyl analogue (1) with [¹⁸F]fluoroethyltosylate in DMSO in the presence of 1.6 equiv of K₂CO₃ in 45 ± 5% yield (EOS). PET shows [¹⁸F]FECUMI-101 binds specifically to 5-HT_1AR enriched brain regions of baboon. The specificity of [¹⁸F]FECUMI-101 binding to 5-HT_1AR was confirmed by challenge studies with the known 5-HT_1AR ligand WAY100635. These findings indicate that [¹⁸F]FECUMI-101 can be a viable agonist ligand for the in vivo quantification of high affinity 5-HT_1AR with PET.     

Comparaison de différentes méthodes de segmentation en TEP/TDM pour le ciblage en radiothérapie des carcinomes épidermoïdes des VADS

IntroductionTo assess interobserver variability for biological target volume (BTV) delineation and to compare the reproductibility of different semiautomatic segmentation methods in pretreatment 18-fluorodeoxyglucose positron emission tomography (PET/CT) of head and neck squamous cell carcinoma (HNSCC).Patients and methodsPatients with histologically proved HNSCC referred to the nuclear medicine service in Brest for pretreatment PET/CT were prospectively included from February 2009 to June 2010. Three nuclear medicine physicians (two specialized in oncology) delineated manually and independently BTV on each primary tumor. Four semiautomatic segmentation methods have been studied; three using a fixed threshold and one applying an adaptive threshold based on the signal-to-background ratio (Daisne). The variability between κ observers and/or methods has been assessed. The concordance between the various BTV intersections and unions has been also assessed.ResultsThirty patients (29M; 1F) were included. The primary site location was oropharynx in six patients, oral cavity in 10 patients, hypopharynx in five patients and larynx in nine patients. A statistically significant global interobserver variability (P = 0.01) was showed, but without statistically difference between the two experienced oncologists (P = 0.15). The maximal concordance of the two experienced observers with the semiautomatic methods was found for the Daisne method (CI = 61.5%; κ = 0.68), expressing a good agreement according to the Landis and Koch criteria, better than with the segmentation method using a fixed threshold with 40% of maximal signal intensity (CI = 52.1%; κ = 0.53).ConclusionOur results suggest the feasibility of achieving HNSCC BTV delineation by PET/CT using semiautomatic methods, in particular those which apply an adaptative threshold but under the supervision of an experienced operator.