The Authors Respond

International audienc

[¹⁸F]FDG positron emission tomography within two weeks of starting erlotinib therapy can predict response in non-small cell lung cancer patients.

International audiencePURPOSE: The aim of this prospective study was to evaluate whether [¹⁸F]FDG-PET/CT, performed within two weeks of starting erlotinib therapy can predict tumor response defined by RECIST 1.1 criteria after 8 weeks of treatment in patients with inoperable (stage IIIA to IV) non-small cell lung cancer patients.PATIENTS AND METHODS: Three [¹⁸F]FDG-PET/CT scans were acquired in 12 patients before (5±4 days) and after 9±3 days (early PET) and 60±6 days (late PET) of erlotinib therapy. Conventional evaluation, including at least chest CT (baseline versus after 8 weeks of treatment), was performed according to RECIST 1.1 criteria. Change in [¹⁸F]FDG uptake was compared with conventional response, progression-free survival (PFS), and overall survival (OS).RESULTS: By using ROC analysis, the Area Under the Curve for prediction of metabolic non-progressive disease (mNP) by early PET was 0.86 (95% CI, 0.62 to 1.1; P = 0.04) at a cut-off of 21.6% reduction in maximum Standardized Uptake Value (SUVmax). This correctly classified 11/12 patients (7 with true progressive disease; 4 with true non-progressive disease; 1 with false progressive disease). Non-progressive disease after 8 weeks of treatment according to RECIST 1.1 criteria was significantly more frequent in patients classified mNP (P = 0.01, Fisher's exact test). mNP patients showed prolonged PFS (HR = 0.27; 95% CI, 0.04 to 0.59; P<0.01) and OS (HR = 0.34; 95% CI, 0.06 to 0.84; P = 0.03). Late PET analysis provided concordant results.CONCLUSION: Morphologic response, PFS and OS survival in non-small cell lung cancer patients can be predicted by [¹⁸F]FDG-PET/CT scan within 2 weeks after starting erlotinib therapy

Infection de prothèse vasculaire : 18TEP-FDG vs scintigraphie aux leucocytes marqués (planaires et TEMP/TDM)

International audienceVascular prosthesis infection is an uncommon but life-threatening complication. Its diagnosis is difficult to establish especially due to the low specificity of computed tomography (CT). The aim of this preliminary study was to compare the diagnostic value of positron emission tomography with18FDG (18FDG-PET) and 99mTc-HMPAO-labeled leukocytes scintigraphy in this indication. 18FDG-PET/CT and 99mTc-HMPAO-labeled leukocytes scintigraphy (planar at 6th and 24th hours after injection + SPECT/CT at the 6th hour) were prospectively performed in 11 patients (total of 22 vascular prosthesis with 14 clinical suspicions of infection). Both scans were retrospectively and blindly assessed by two independent nuclear medicine physicians. Interpretation was based on visual analysis. The gold standard was bacteriology findings or clinical follow-up greater than 6 months. Eight prostheses were considered as infected. PET found eight true-positive and one false-positive. Scintigraphy found eight true-positive and no false-positive. A focal or heterogeneous FDG-uptake higher or equal than hepatic uptake was considered as positive in PET. A focal prosthetic activity, stable or increased at the 24th hour was considered as positive in labeled leukocyte scintigraphy. SPECT/CT gave accurate anatomic localization and differentiated clearly infections of soft tissues from those of prostheses. 18FDG-PET could be performed in first-line in suspicion of vascular prosthesis infection. In litigious cases, a99mTc-HMPAO-labeled leukocytes scintigraphy in association with SPECT/CT could bring additional arguments for infection diagnosis.L’infection de prothèse vasculaire est une complication rare, mais grave. Son diagnostic est difficile, notamment car l’imagerie conventionnelle est peu spécifique. Le but de cette étude préliminaire était de comparer l’apport diagnostique de la tomographie par émission de positons au 18FDG (TEP-18FDG) à celui de la scintigraphie aux leucocytes marqués à l’HMPAO-99mTc dans cette indication. Réalisation prospective d’une TEP-18FDG couplée au scanner et d’une scintigraphie aux leucocytes marqués (planaires à la sixième et 24e heures&nbsp;+&nbsp;tomographie par émission monophotonique couplée à la tomodensitométrie [TEMP-TDM] à la sixième heure) chez 11&nbsp;patients (22&nbsp;prothèses au total avec suspicion clinique d’infection pour 14&nbsp;d’entre elles). Relecture rétrospective, en aveugle, des examens par deux médecins nucléaires. Interprétation basée sur une analyse visuelle de l’intensité et de l’aspect de la fixation des prothèses. L’étalon de référence était la bactériologie ou un suivi supérieur à six mois. L’infection de prothèse était retenue dans huit cas. La TEP retrouvait huit vrais positifs et un faux positif et la scintigraphie, huit vrais positifs et aucun faux positif. Une hyperfixation focale ou hétérogène supérieure ou égale à la fixation hépatique était retenue comme positive en TEP. Une hyperfixation focale stable ou augmentée à 24&nbsp;heures était retenue comme positive pour la scintigraphie. La TEMP-TDM a permis de localiser avec précision les infections limitées aux tissus mous. La TEP-18FDG pourrait être effectuée en première intention dans les suspicions d’infection de prothèses vasculaires et complétée, en cas de doute, par une scintigraphie aux leucocytes avec TEMP-TDM.</p

Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats

International audienceLipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives

International audienceRhenium-188 (Re-188) is a high energy beta-emitting radioisotope with a short 16.9 h physical half-life, which has been shown to be a very attractive candidate for use in therapeutic nuclear medicine. The high beta emission has an average energy of 784 keV and a maximum energy of 2.12 MeV, sufficient to penetrate and destroy targeted abnormal tissues. In addition, the low-abundant gamma emission of 155 keV (15%) is efficient for imaging and for dosimetric calculations. These key characteristics identify Re-188 as an important therapeutic radioisotope for routine clinical use. Moreover, the highly reproducible on-demand availability of Re-188 from the W-188/Re-188 generator system is an important feature and permits installation in hospital-based or central radiopharmacies for cost-effective availability of no-carrier-added (NCA) Re-188. Rhenium-188 and technetium-99 m exhibit similar chemical properties and represent a "theranostic pair." Thus, preparation and targeting of Re-188 agents for therapy is similar to imaging agents prepared with Tc-99m, the most commonly used diagnostic radionuclide. Over the last three decades, radiopharmaceuticals based on Re-188-labeled small molecules, including peptides, antibodies, Lipiodol and particulates have been reported. The successful application of these Re-188-labeled therapeutic radiopharmaceuticals has been reported in multiple early phase clinical trials for the management of various primary tumors, bone metastasis, rheumatoid arthritis, and endocoronary interventions. This article reviews the use of Re-188-radiopharmaceuticals which have been investigated in patients for cancer treatment, demonstrating that Re-188 represents a cost effective alternative for routine clinical use in comparison to more expensive and/or less readily available therapeutic radioisotopes

Effective Targeting Of Endometrial Tissue By 16α-[18f]Fluoro-17β-Œstradiol ([18f]-Fes): Preliminary Results In The Diagnosis Of Endometriosis

International audienc

Imagerie phénotypique et peptides radiomarqués au gallium-68 : au-delà des analogues de la somatostatine

International audienceReceptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin. However, other radiolabeled analogs have also been developed and assessed in vitro and in vivo and some of them are already in clinical use. For instance, radiolabeled analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP), cholecystokinin (CCK), integrins… This review focuses on gallium-68&nbsp;radiolabeled peptides developed for PET imaging, except for somatostatin analogs, which are discussed in another article.Le ciblage de récepteurs avec des peptides radiomarqués est devenu très important en oncologie nucléaire au cours de ces dernières années. Les peptides les plus fréquemment utilisés en clinique sont les analogues de la somatostatine. Cependant, d’autres analogues radiomarqués ont également été développés et évalués in vitro et in vivo et pour certains déjà en clinique. Il s’agit par exemple de l’alpha-melanocyte-stimulating hormone (alpha-MSH), de la neurotensine, du peptide intestinal vasoactif (VIP), de la bombésine, de la substance P (SP) et de la cholécystokinine (CCK), des intégrines… Cette revue se focalise sur les peptides radiomarqués au gallium-68, développés pour l’imagerie TEP, en dehors des analogues de la somatostatine, qui sont discutés dans un autre article.</p

Isotopic scintigraphy combined with computed tomography: A useful method for investigating inefficiency of intrathecal baclofen

International audienceBackground: Intrathecal baclofen infusion is an established method for the treatment of generalized and disabling spasticity. The most frequent technical problems are due to catheter&nbsp;/pump disconnections, but diagnosis of dysfunction may be difficult.CASE REPORT:&nbsp;We report here the case of a 53-year-old woman with spastic paraplegia treated with intrathecal baclofen. Spasticity remained uncontrolled despite a gradual increase in baclofen dosage. On plain radiographs the distal end of the catheter was found to be pointing downwards with the catheter tip at level L5 and no apparent disconnection or failure. Indium111 diethylenetriamine penta-acetic acid (DTPA) scintigraphy combined with computed tomography revealed that the activity of the radioisotope was highest next to the first sacral vertebra and that there was no leakage. Radioisotope activity above the lumbar level was very low. The catheter tip was therefore repositioned to level T7. One month later, spasticity was well controlled and a second scintigraphy confirmed high activity of intrathecal radioisotope up to the basal cisterns.Discussion: The combination of Indium111 DTPA scinti-graphy with computed tomography allows anatomical and functional investigation of intrathecal drug administration. In this case report this approach showed that the inefficiency of intrathecal baclofen was due to the caudal orientation of the catheter.</p

Effective Targeting Of Endometrial Tissue By 16α-[18f]Fluoro-17β-Œstradiol ([18f]-Fes): Preliminary Results In The Diagnosis Of Endometriosis

International audienc

Ciblage des tissus endométriaux par la 16α-[18F]fluoro-17β-œstradiol (PET-[18F]FES) : résultats préliminaires dans le diagnostic de l’endométriose

International audienceObjectifsLa tomographie par émission de positons (TEP) à la 16α-[18F]fluoro-17β-œstradiol ([18F]FES) permet d’évaluer in vivo la densité tissulaire en récepteurs aux œstrogènes (RE). Cet article rapporte les premiers cas dans le diagnostic de l’endométriose.Patientes et méthodesDans le cadre de la mise en place du PHRC ENDOTEP, quatre patientes présentant des signes cliniques et morphologiques (échographie pelvienne ± IRM) suspects d’endométriose ont bénéficié d’une TEP-[18F]FES avant cœlioscopie (analyse macroscopique et analyse histologique et immunohistochimique de l’expression en RE des lésions prélevées).RésultatsChez les quatre patientes, le diagnostic d’endométriose a été retenu macroscopiquement et après analyse histologique d’au moins une lésion. Aucune captation de [18F]FES par les lésions d’endométriose n’a été observée chez les trois premières patientes sous traitement œstroprogestatif. La quatrième patiente non traitée et en première partie de cycle menstruel lors de la réalisation de la TEP-[18F]FES présentait en revanche une hyperfixation d’une lésion d’endométriose confirmée en cœlioscopie.ConclusionNous rapportons le premier cas de fixation de [18F]FES par une lésion d’endométriose. À travers le projet ENDOTEP, les performances de la TEP-[18F]FES pour le diagnostic d’endométriose seront évaluées chez des patientes ne recevant pas de traitement hormonal.ObjectifsLa tomographie par émission de positons (TEP) à la 16α-[18F]fluoro-17β-œstradiol ([18F]FES) permet d’évaluer in vivo la densité tissulaire en récepteurs aux œstrogènes (RE). Cet article rapporte les premiers cas dans le diagnostic de l’endométriose.Patientes et méthodesDans le cadre de la mise en place du PHRC ENDOTEP, quatre patientes présentant des signes cliniques et morphologiques (échographie pelvienne ± IRM) suspects d’endométriose ont bénéficié d’une TEP-[18F]FES avant cœlioscopie (analyse macroscopique et analyse histologique et immunohistochimique de l’expression en RE des lésions prélevées).RésultatsChez les quatre patientes, le diagnostic d’endométriose a été retenu macroscopiquement et après analyse histologique d’au moins une lésion. Aucune captation de [18F]FES par les lésions d’endométriose n’a été observée chez les trois premières patientes sous traitement œstroprogestatif. La quatrième patiente non traitée et en première partie de cycle menstruel lors de la réalisation de la TEP-[18F]FES présentait en revanche une hyperfixation d’une lésion d’endométriose confirmée en cœlioscopie.ConclusionNous rapportons le premier cas de fixation de [18F]FES par une lésion d’endométriose. À travers le projet ENDOTEP, les performances de la TEP-[18F]FES pour le diagnostic d’endométriose seront évaluées chez des patientes ne recevant pas de traitement hormonal