Radiothérapie interne vectorisée par 177Lu-PSMA-617 de l’adénocarcinome prostatique métastatique résistant à la castration : à propos d’un cas et revue de la littérature

The prostate-specific membrane antigen (PSMA) is a type II glycoprotein which is over-expressed in prostate cancer tissue, especially in high grade tumours, metastatic disease, as an effect of androgen-deprivation therapies and in castrate-resistant prostate cancer (CRPC). Recent studies about radioligand therapy using PSMA ligands labeled with lutetium-177 (¹⁷⁷Lu) in CRPC patients have suggested its interest as a third line of treatment after second generation anti-androgens and chemotherapy by taxane. We present the case of a CRPC patient who was treated by iterative radioligand therapy using PSMA-617 ligand labeled with ¹⁷⁷Lu. This case illustrates on the one hand the efficacy of the treatment, and on the other hand the fragility of the patients who are at an advanced stage of their disease. Then we present a short review of the literature on this topic, focusing on the published efficacy and tolerance of ¹⁷⁷Lu-PSMA radioligand therapy of CRPC patients.     

Unusual spread of the follicular thyroid carcinoma,metastases to liver and pancreas

We report a multimetastatic follicular thyroid carcinoma(FTC) with match lesions between ¹⁸F-FDG PET/CT and post-treatment ¹³¹I imaging. The patient had a history of thoracic vertebra corpectomy surgery and liver tru-cut biopsy; both resulted in metastases of FTC. After total thyroidectomy surgery, the patient was referred to the ¹⁸F-FDG PET/CT to investigate other possible metastatic foci. ¹⁸F-FDG PET/CT showed increased FDG uptakes on a cervical lymph node, bones, lung, liver, and pancreas. After treatment of ¹³¹I, post-treatment iodine scintigraphy demonstrated iodine uptakes in the same areas as the ¹⁸F-FDG PET/CT scan and at the thyroid bed. All the matched lesions were concluded as a spread of the FTC. Here we describe an infrequent differentiated thyroid carcinoma case with metastases to the liver and pancreas. This case report also highlights the importance of ¹⁸F-FDG PET/CT in determining the extent of thyroid cancer.     

Aberrant positive metaiodobenzylguanidine (MIBG) scan in a patient with gastrointestinal stromal tumor

¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy is an effective means of diagnosing chromaffin-cell tumors such as pheochromocytoma. We report a very rare case of a 45-year-old patient with large intra-abdominal mass and elevated urinary normetanephrines. ¹²³I-MIBG scintigraphy showed mild MIBG uptake. Although initial findings suggested a pheochromocytoma, histologic examination along with immunohistochemical staining revealed features suggestive of gastrointestinal stromal tumor (GIST).     

Paramètres TEP/TDM à la 18F-Fluorocholine prédictifs de la toxicité hématologique du 223Radium dans les cancers prostatiques métastatiques osseux résistant à la castration

Background

²²³RadiumCl₂ (²²³Ra) demonstrated in the study ASLYMPCA an improved median overall survival in patients with bone metastases and castration resistant prostate cancer. This treatment is expensive and carries a risk for hematologic toxicity. The main objective of our work was to study a biomarker on ¹⁸F-FCH PET/CT to predict the risk of hematological complications of ²²³Ra. The impact of ¹⁸F-FCH PET/CT on the initial management of ²²³Ra therapy was also investigated.

Combination of [68Ga]Ga-PSMA PET/CT and [18F]FDG PET/CT in demonstrating dedifferentiation in castration-resistant prostate cancer

Aim of the studyIn this study, we aimed to determine the factors affecting increased glucose metabolism, which is one of the dedifferentiation mechanisms, by using [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA PET/CT in patients with castration-resistant prostate cancer (CRPC).Materials and methodNinety-three patients with CRPC were included in the study. Gleason score (GS), and total PSA and free PSA levels of the patients were recorded. Patient- and organ-based evaluations were performed according to the lesion uptakes as follows: score 0: PSMA (-) FDG (-), score 1: PSMA (+) FDG (-), score 2: PSMA (+) FDG (+) (FDG < PSMA), score 3: PSMA (+) FDG (+) (FDG = PSMA), score 4: PSMA (+) FDG (+) (FDG > PSMA), and score 5: PSMA (-) FDG (+). scores 1 and 2 were classified as group 1, and scores 3 to 5 were classified as group 2.ResultsThe median age of our patients was 70 (51–88) years. Eighty-eight patients (94.6%) were PSMA-positive, 78 patients (83.8%) were FDG-positive, and 89 patients (95.6%) were or PSMA or FDG positive. When the two groups were compared in terms of patient-based parameters, the median age and GS were found to be significantly higher in group 2. ROC analyses revealed that age and GS were significant in predicting group 2.ConclusionSince glucose metabolism can increase in CRPC patients with advanced age and high GS, we recommend combining [¹⁸F]FDG PET/CT with [⁶⁸Ga]Ga-PSMA PET/CT in routine clinical practice in order to identify this patient subset and refer them to additional therapies.     

Répartiteur de dose des médicaments radiopharmaceutiques : contrôle qualité sur deux sites hospitaliers et comparaison avec la législation en vigueur en France

An increasing number of nuclear medicine departments are equipped with automated measurement systems for the preparation of radiopharmaceuticals, with the main aim of minimising technician's irradiation. However, the automatic measurement of the patient activity differs from the manual measurement in material and method. In this context, the objective of the present study was to test the performances of one of these systems, the Unidose by TRASIS^®, in two newly equipped hospitals. The particularity of these systems is they are made up of two dose calibrators: the entrance calibrator (well chamber) and the exit calibrator (probe). Controls were performed on both of these dose calibrators. The results obtained, as well as the methodology employed, were then compared with the regulatory requirements in France. The results found are coherent between the two sites and have highlighted several non-conformities compared to the current regulations, part of which concerning the carpule dose calibrator, which is actually a probe. These results raise the question of a suitable regulation for the new automated measurement systems in nuclear medicine.     

Distribution of (14C)MCA and its derivatives in mouse tissues (author's transl)

Distribution of [¹⁴C]MCA and its derivatives in mouse tissuesThe distribution of radioactivity due to 3-methylcholanthrene (MCA) and/or its metabolites was evaluated in different organs of mothers, foetuses and newborns at 6 and 60–66 h following a single intragastric administration of 1 mg of [¹⁴C]MCA to pregnant CF-1 mice. The extent of bound [¹⁴C]MCA nd/or its metabolites to nuclear and cytoplasmic proteins was evaluated in organs which were proven to be either susceptible (lung) or non-susceptible (kidney) to the carcinogenic effect of MCA. The present data indicate a slightly higher level of free and bound MCA in the subcellular fractions of the lung than in the kidney and concurrently a higher level of covalently bound MCA to the nuclear DNA in the lungs than in the kidney.     

Late Cretaceous radiolarian biochronology of the Pedro Brand section,Tireo Group,eastern Central Cordillera,Dominican Republic: A contribution to the stratigraphy of the Caribbean Large Igneous Province

The Tireo Group in the eastern Central Cordillera (Dominican Republic) is part of the Jarabacoa Block, composed of a Pacific-type Jurassic ocean floor (Loma La Monja, overlain by the El Aguacate ribbon Chert), intruded and overlain by an early CLIP (Carribean Large Igneous Province)-type plateau, the Duarte Complex, which is in turn unconformably overlain by arc-type rocks of the Tireo Group. This group exhibits a 3-km thick sequence of arc-related volcanic and volcano-sedimentary rocks, including tuffaceous chert and mudstone studied for radiolarians in this paper. The Siete Cabezas Formation, considered to be the last Campanian–Maastrichtian CLIP-type volcano-sedimentary sequence, overlies the Tireo Group. A controversy about earlier radiolarian dating of the Tireo Group, considered until now as part of the Siete Cabezas Formation, encouraged us to study a well-exposed section located 3 km NE of Pedro Brand village. Seven samples of laminated siliceous mudstones and cherts yielded around 40 common and well-preserved radiolarian taxa. Based on maximum ranges of taxa published in several regional zonations and on a comparison with a Turonian–Coniacian sample calibrated by planktonic foraminifera (the Deva Beds from Romania), we determine a Turonian–Coniacian age for the Pedro Brand section. A ⁴⁰Ar–³⁹Ar whole rock age of 75.1 ± 1.1 Ma, obtained in a basalt dyke crosscutting the radiolarian bearing rocks, provides a Late Campanian consistent minimum age for the pelagic–hemipelagic Pedro Brand section. Including the re-interpretation of earlier radiolarian work, we conclude that the studied rocks of the Tireo Group are older than the Maastrichtian ⁴⁰Ar–³⁹Ar ages on plagioclase of the Siete Cabezas Formation. The studied dyke in the Pedro Brand section geochemically resembles the overlying Siete Cabezas and Pico Duarte basalts and could be a feeder dyke of those. However, a tectonic superposition of the Siete Cabezas cannot be excluded, since earlier ⁴⁰K–⁴⁰Ar basalt ages of this unit are Aptian–Albian and Cenomanian–Turonian. The Jarabacoa Block is considered as the most complete outcrop section of Pacific ocean crust overlain by a first (Aptian–Albian) phase of CLIP-type activity, followed by the development of a Cenomanian–Santonian intraoceanic arc, which is in turn overlain by a late Campanian–Maastrichtian CLIP-like phase.     

Peptide receptor radionuclide therapy of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): From literature to practice

Well differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by the overexpression of specific biomarkers, especially somatostatin receptors subtype 2. Somatostatin receptor scintigraphy and currently, positron emission tomography using ⁶⁸Ga-labeled-somatostatin analogs are considered the gold standard for functional imaging of GEP-NETs. They are complementary to CT scan and to MRI, for the staging and restaging of these tumors and are useful to select patients for peptide receptor radionuclide therapy (PRRT), in a theranostic approach. Somatostatin analogues, radiolabeled with the beta-emitting radionuclides lutetium-177 and yttrium-90, have been developed for PRRT of GEP-NETs. The efficacy of this treatment depends on the intensity of uptake on pre-therapeutic scan, the extent of hepatic involvement, and a preserved global health status. Toxicity, mainly hematologic and renal can be reduced by a rigorous selection of patients and co-infusion of amino-acids. PRRT became possible since 2013 in some specialized centers in France, by the way of clinical research programs and temporary authorization from the Agence nationale de sécurité du médicament et des produits de santé to use PRRT. This decision took place after the communication of preliminary results of the NETTER-1 study, which confirmed the efficacy of LUTATHERA^® in the treatment of midgut NETs. A marketing authorization for this radiopharmaceutical is expected in France in 2017. This article reports the main data of the literature on the development of PRRT and its current use in France. It also reviews the indications and the side effects of the treatment, and presents the perspective of optimization of this promising therapeutic approach for the coming years. The other therapeutic options in GEP-NETs are also presented.     

Value of 18FDG PET for prediction of therapeutic response in HER2+ breast cancer: Interim analysis

¹⁸F-FDG PET is recommended for the initial staging of locally advanced breast cancer. Studies have shown the prognostic value of ¹⁸F-FDG PET for staging, but its ability to predict pathological complete response remains uncertain. Our objective was to determine the predictive value of early therapeutic evaluation by ¹⁸F-FDG PET for HER2-positive breast cancer patients. We studied a subpopulation of the prospective and multicentric French NeoTOP trial, at interim analysis. All patients were eligible for neoadjuvant chemotherapy. A ¹⁸F-FDG PET was performed at baseline and then after one cycle of neoadjuvant treatment. ¹⁸F-FDG PET were studied by three conventional methods (two visuals and one quantitative) and by textural analysis. Complete pathological response on surgical samples corresponded to grades 1/2 of Chevallier's classification and no responders corresponded to grades 3/4 of Chevallier. Pathological results were available for 21 patients. SUV_max decreased by 55% after one cycle of chemotherapy. No difference between groups was found with visuals, conventional quantitative and textural analysis of tumour uptake evaluations. Early therapeutic evaluation by ¹⁸F-FDG PET for HER2-positive breast cancer was not predictive of pathological therapeutic response after neoadjuvant treatment, with conventional study or textural analyses in this interim analysis.     

Inguinal lymphadenopathy of cat-scratch disease mimicking malignant hemopathy on 18FDG-PET/CT

18-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) is a valuable imaging technique for the diagnosis and staging of malignant pathologies. Nevertheless, false positive exams exist, especially in the case of infectious or inflammatory diseases. We report a case of a 39-year-old man who presented a cat-scratch disease (CSD), which was revealed through hypermetabolic inguinal lymphadenopathy on ¹⁸FDG-PET/CT mimicking malignant hemopathy. Finally, biopsy and PCR analysis revealed Bartonella henselae infection.     

Compétitivité pour l'infection entre souches deRhizobium meliloti: Role de la mobilité

Resumé A partir de la souche deR. meliloti Ve 26 mobile et chimiotactique, un mutant non mobile (mob⁻) et un mutant hyper-mobile (mob⁺) ont été isolés. L'importance du r?le de la mobilité dans les phénomènes d'infection et de nodulation lors d'inoculations mixtes réalisées en miniserre expérimentale, est montrée: le mutant Ve 26 mob⁺ forme 86% et 48% de nodules respectivement quand il est inoculé en mélange avec le mutant Ve 26 mob⁻ ou avec la souche 2011 (non mobile par rapport au mutant Ve 26 mob⁺). L'inoculation mixte avec le mutant Ve 26 mob⁻ et la souche 2011 deR. meliloti, en utilisant différents rapports de concentrations, a permis de montrer qu'il existe entre ces souches un effet antagoniste pour l'infection.      

Intérêt de la TEP/TDM au 18F-FDG dans la neurofibromatose de type 1, expérience du centre national de référence Henri-Mondor sur 10 ans

ObjectiveMalignant peripherals nerve sheath tumours (MPNST) are one of the leading causes of death in neurofibromatosis type 1 (NF1). Given the temporal and spatial multiplicity of suspicious lesions, the histological diagnosis of certainty might require iterative and decaying surgical procedure. Our objective was to determine the threshold values of metabolic metrics determined on ¹⁸F-FDG PET/CT (SUV_max, total lesion glycolysis [TLG], total metabolic tumour volume [TMTV], tumour-to-liver [T/L] ratio and heterogeneity index [HI]) in order to distinguish at best MPNST from benign lesion (simple neurofibromas [NF] or dysplastic NF).Patients and methodsHundred and seven patients from the national reference centre of NF1 Henri-Mondor, clinically suspects of TMGN, underwent 160 ¹⁸F-FDG PET/CT over a period of 10 years, between 2005 and 2015. The hypermetabolics lesions identified on ¹⁸F-FDG PET/CT were confronted with pathological analysis or clinico-radiological and metabolic follow-up of more than 6 months.ResultsFour hundred and eight hypermetabolics lesions were identified, of which 112 were histologically confronted with 38 simple NF, 29 dysplastic NF, 39 TMGN and 6 incidentalomas. The remaining 296 hypermetabolics lesions experienced a median follow-up of 40.4 months [13.5–137 months]. The optimal cut-off values for malignant lesions, determined by ROC curves, were in order of decreasing performance: T/L ratio > 2.03 (sensitivity 96%, specificity 88%); SUVmax > 4.74 (sensitivity 93%, specificity 86%); TLG > 172 (sensitivity 84%, specificity 76%); TMTV > 53.5 (sensitivity 83%, specificity 68%); HI > 1.63 (sensitivity 84%, specificity 54%).Conclusions¹⁸F-FDG PET/CT is a powerful diagnostic and prognostic tool in the management of TMGN. Metabolic metrics allow with good sensitivity and specificity to identify lesions transformed into TMGN. The advent of PET/MRI will undoubtedly allow in the near future to reinforce the diagnostic and prognostic performances for the detection of transformations of neurofibromas in TMGN.     

Radioiodine-131 therapy (RIT) in benign thyroid diseases: Personalized prescription based on objectives with optional use of pharmacological modulators

¹³¹I therapy (RIT) in benign thyroid diseases is the oldest and most currently used application of internal radiotherapy. With the new molecular ¹²³I-TS images one may identify 15 presentations that can benefit from RIT. With three groups of activity determination corresponding to a dozen approaching protocols, several judgmental criteria (eu-, hypo-, hyperthyroidism, relapses etc.) and varying timeframes to assess the success, a “best method of activity calculation” makes little sense. Four clinical objectives must be first identified (goal): antitoxic (euthyroidism), ablative (hypothyroidism), reductive (to reduce a targeted volume) and preventive (to prevent progression from compensated to overt hyperthyroidism) ¹³¹I-RIT. A dose response relationship as regards the target volume reduction is firmly established in the short term (1-year) and explains the clinical outcome in Thyroid Functional Autonomy (TFA). In Grave's disease (GD), other factors may interfere that make the long-term function less predictable. Pharmacological modulators of ¹³¹I-RIT such as antithyroid drugs (ATDs) and LT3 must be skillfully handled. ATDs interfere with iodine kinetics, enhance the heterogeneity of the spatial dose deposition and diminish the accuracy of absorbed dose deposition, especially when using poorly controlled dosimetric approaches. Short LT3 administration suppresses TSH that allows direct targeting of the autonomously functioning thyroid tissue. The three main groups and variants of activity calculation are presented in detail. Calculating the activity allows a 50% average reduction in the ¹³¹I administered dose. Medical strategy should favour the informed patient's choice, after excluding the rare medical causes prompting discussion of an ablative approach. In TFA, low occurrence of hypothyroidism is the rule provided the treatment be given with a TSH < 0.1 mU/L, spontaneously or after LT3 suppression (compensated variety). In GD a long-term remission is rare (< 30%) and should be thoroughly discussed since it leads to euthyroidism in approximately 50% after a 12-year follow-up. Depending on the etiology (GD/TFA) and the 4 clinical goals, ¹³¹I RIT planning is presented with optional choice of a patient adapted method of activity calculation and appropriate management of pharmacological modulators.     

Alcaloïdes des ecorces de racines de Crioceras dipladeniiflorus

Eight alkaloids have been isolated from the root bark of Crioceras dipladeniiflorus. Five of them are new: Δ¹⁴-vincamine (I) epi-16 Δ¹⁴-vincamine (II) 12-methoxy-δ ¹⁴-vincamine (V) apo Δ¹⁴- vincamine (VI), and ditabersonine (VII), a dimeric alkaloid; the three others are known, voaphylline (III), tabersonine, (IV), and vobtusine (VIII).     

Performance de la 18FDG-TEP dans le dépistage de paragangliome chez des patients porteurs d’une mutation SDHx

ObjectiveTo evaluate the performance of ¹⁸FDG-PET/CT for detecting infra-clinic paraganglioma (PGL) in SDHx mutation carriers (relatives).Patients and methodsSixty-six patients, from 13 distinct families underwent a genetic testing on the SHD genes between 2003 and 2012. Among the 45 patients with a mutation, 30 with a ¹⁸FDG-PET performed at initial work-up were included in this retrospective study. A gadolinium-enhanced magnetic resonance angiography of the neck (angio-MR) was performed in all cases, a thoracoabdominal-pelvic contrast-enhanced computed tomography (TAP-CT) in 25 cases, a TAP-MR in 20 cases, a ¹²³I-metaiodo-benzylguanidine scintigraphy (¹²³I-MIBG) in 20 cases and a somatostatin receptor scintigraphy (SRS) in 20 cases. Gold standard was histologic or composite (confirmation by another imaging method and follow-up).ResultsA tumor was found in five subjects: 2 abdominal PGL, 1 pheochromocytoma and 2 PGL of the neck. The sensitivity of ¹⁸FDG-PET was 100 %, of SRS was 80 %, of ¹²³I-MIBG was 60 % and of anatomical imaging (association between angio-MR of the neck and TAP-CT and/or TAP-MR) was 100 %. Three false positive lesions were described: 2 with the ¹⁸FDG-PET imaging and 1 with the TAP-MR technique.Conclusion¹⁸FDG-PET/CT is an excellent tool for screening SDHx relatives and should be completed by an angio-MR of the neck if suspicion of abnormality. Association of angio-MR of the neck and TAP-MR has the advantage of being a non-irradiating imaging method but with limited access in some countries.     

Caractérisation des adénopathies médiastinales en TEP/TDM au 18F-FDG

The mediastinum is a complex anatomical region located at the junction of the cervical, thoracic and abdominal regions. It is an important lymphatic gateway that has an impact in many pathologies with nodal involvement and for which ¹⁸F-FDG PET/CT is a central examination. In this review article, we propose to recall the normal and pathological lymphatic drainage, mediastinum anatomy, the International Association for the Study of Lung Cancer (IASLC) lymph node classification and its implications in lung cancer. Then we will detail the morphological and metabolic characteristics, principal etiologies and the procedures to access mediastinal lymph nodes.     

Is there a place for nuclear medicine in the radioembolization of liver tumors?

This is purposely an ultraprovocative title for the broad nuclear medicine community (including radiophysics and radiopharmacy) which leads us to ask questions about how we should correctly use ⁹⁰Yttrium (MSY90) microspheres in the treatment of liver tumors.     

Rythme Circadien endogène d'émergence et d'activité natatoire chez i'isopode profond Cirolana borealis lilljeborg

L'Isopode profond Cirolana borealis présente en milieu expérimental un rythme circadien endogène net d'émergence du sédiment, de géonégativité, et d'activité natatoire. Le rythme a pu être enregistré durant plus de 60 jours consécutifs en obscurité constante. Il se manifeste chez les animaux conditionnés à un éclairement de surface (100 à 10^‐5 μW.cm^‐2), chez ceux conditionnés à éclairement très réduit (10^‐4 à 10^‐11 μW.cm^‐2), et chez ceux prélevés à ‐ 400 m, et immédiatement expérimentés. La phase d'activité, de durée variable selon les individus, est centrée sur le crépuscule. La période et l'amplitude sont sujettes à de fortes variations individuelles. Généralement inférieure à 24 h chez les animaux conditionnés au laboratoire, la période est le plus souvent supérieure à 25 h chez les animaux provenant directement du milieu naturel. La synchronisation semble essentiellement assurée par les variations lumineuses nycthémérales: un éclairement de valeur diurne provoque une géopositivité permanente et, le plus souvent, un enfouissement au moins partiel des individus, même durant la phase d'activité.