Interest of FDG-PET in the Management of Mantle Cell Lymphoma

FDG-PET changed response assessment and therapy strategy in diffuse large B-cell lymphoma and Hodgkin disease lymphoma. The value of FDG-PET evaluation in MCL has not been extensively studied and a recent expert consensus highlighted the need for more studies addressing this question. Data of the literature show the value of FDG-PET at baseline in patients with MCL, underlining the good sensitivity of this examination for the initial staging of this pathology, but also the potential impact of semi-quantitative analysis in this indication. The determination of SUVmax at diagnosis might indeed provide important prognostic information. Some studies also suggest the potential value of early and end-of-treatment metabolic assessment in MCL, but these results need to be validated in standardized prospective studies. These results also underlie the need to integrate FDG-PET results into MCL treatment strategy to improve disease management in identifying patients who might benefit from more intensive therapy

Interest of Pet Imaging in Multiple Myeloma

The interest of 18Fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging in the management of patients with multiple myeloma (MM) for the workup at diagnosis and for therapeutic evaluation has recently been demonstrated. FDG-PET is a powerful imaging tool for bone lesions detection at initial diagnosis with high sensitivity and specificity values. The independent pejorative prognostic value on progression-free survival (PFS) and overall survival (OS) of baseline PET-derived parameters (presence of extra-medullary disease (EMD), number of focal bone lesions (FLs), and maximum standardized uptake values [SUVmax]) has been reported in several large independent prospective studies. During therapeutic evaluation, FDG-PET is considered as the reference imaging technique, because it can be performed much earlier than MRI which lacks specificity. Persistence of significant FDG uptake after treatment, notably before maintenance therapy, is an independent pejorative prognostic factor, especially for patients with a complete biological response. So FDG-PET and medullary flow cytometry are complementary tools for detection of minimal residual disease before maintenance therapy. However, the definition of PET metabolic complete response should be standardized. In patients with smoldering multiple myeloma, the presence of at least one hyper-metabolic lytic lesions on FDG-PET may be considered as a criterion for initiating therapy. FDG-PET is also indicated for initial staging of a solitary plasmacytoma so as to not disregard other bone or extra-medullary localizations. Development of nuclear medicine offer new perspectives for MM imaging. Recent PET tracers are willing to overcome limitations of FDG. (11)C-Methionine, which uptake reflects the increased protein synthesis of malignant cells seems to correlate well with bone marrow infiltration. Lipid tracers, such as Choline or acetate, and some peptide tracers, such as (68) Ga-Pentixafor, that targets CXCR4 (chemokine receptor-4, which is often expressed with high density by myeloma cells), are other promising PET ligands. 18F-fludarabine and immuno-PET targeting CD138 and CD38 also showed promising results in preclinical models

Improvement of Radioimmunotherapy Using Pretargeting

During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabeled monoclonal antibodies and receptor binding agents. Conventional radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor, and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics. Pretargeting techniques (pRIT) are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb) from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA, and bispecific antibody-hapten bindings. pRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta, and Auger emitters) with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT

Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors

International audienceBackgroundOverexpression of syndecan-1 (CD138) in breast carcinoma correlates with a poor prognosis and an aggressive phenotype. The objective of this study was to evaluate the potential of targeting CD138 by immuno-PET imaging and radioimmunotherapy (RIT) using the antihuman syndecan-1 B-B4 mAb radiolabeled with either 124I or 131I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line.MethodThe immunoreactivity of 125I-B-B4 (80%) was determined, and the affinity of 125I-B-B4 and the expression of CD138 on MDA-MB-468 was measured in vitro by Scatchard analysis. CD138 expression on established tumors was confirmed by immunohistochemistry. A biodistribution study was performed in mice with subcutaneous MDA-MB-468 and 125I-B-B4 at 4, 24, 48, 72, and 96 h after injection and compared with an isotype-matched control. Tumor uptake of B-B4 was evaluated in vivo by immuno-PET imaging using the 124I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with 131I-B-B4 and the RIT efficacy evaluated.Results 125I-B-B4 affinity was in the nanomolar range (Kd = 4.39 ± 1.10 nM). CD138 expression on MDA-MB-468 cells was quite low (Bmax = 1.19 × 104 ± 9.27 × 102 epitopes/cell) but all expressed CD138 in vivo as determined by immunohistochemistry. The tumor uptake of 125I-B-B4 peaked at 14% injected dose (ID) per gram at 24 h and was higher than that of the isotype-matched control mAb (5% ID per gram at 24 h). Immuno-PET performed with 124I-B-B4 on tumor-bearing mice confirmed the specificity of B-B4 uptake and its retention within the tumor. The MTD was reached at 22.2 MBq. All mice treated with RIT (n = 8) as a single treatment at the MTD experienced a partial (n = 3) or complete (n = 5) response, with three of them remaining tumor-free 95 days after treatment.ConclusionThese results demonstrate that RIT with 131I-B-B4 could be considered for the treatment of metastatic triple-negative breast cancer that cannot benefit from hormone therapy or anti-Her2/neu immunotherapy. Immuno-PET for visualizing CD138-expressing tumors with 124I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging

Теоремы сходимости и компактности для уравнений Бельтрами

Доведено ряд теорем збіжності та компактності класів регулярних розв'язків вироджених рівнянь Бельтрамі з обмеженнями інтегрального типу на дилатацію.A number of convergence and compactness theorems for classes of regular solutions of the degenerate Beltrami equations with restrictions of the integral type on a dilatation is proved

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen

Les anticorps radiomarqués pour le traitement des cancers

Les anticorps radiomarqués ont maintenant fait leurs preuves dans le traitement des lymphomes malins non hodgkiniens de phénotype lymphocytaire B. D’autres maladies cancéreuses s’avèrent plus difficiles à traiter, que les cellules soient trop dispersées pour un traitement avec un émetteur de particules β- peu efficaces contre des cellules isolées (cas des leucémies par exemple) ou que ces cellules, comme dans la plupart des tumeurs solides, soient radiorésistantes. Des approches nouvelles, préciblage, utilisation d’atomes émetteurs de particules α ou d’électrons Auger sont en passe d’apporter des solutions convaincantes et la radio-immunothérapie devrait trouver sa place dans une approche rationnelle du traitement des cancers

L'imagerie phénotypique du cancer du sein

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM)National audience

Innovative radiopharmaceuticals in oncology and neurology

The aim of this Research Topic was to assemble a series of articles describing basic, preclinical and clinical research studies on radiopharmaceuticals and nuclear medicine. The articles were written by attendees of the third Nuclear Technologies for Health Symposium (NTHS, 10th-11th March 2015, Nantes, Frances) under the auspices of the IRON LabEx (Innovative Radiopharmaceuticals for Oncology and Neurology Laboratory of Excellence). This French network, gathering approximately 160 scientists from 12 academic research teams (Funded by “investissements d’Avenir”), fosters transdisciplinary projects between teams with expertise in chemistry, radiochemistry, radiopharmacy, formulation, biology, nuclear medicine and medical physics. The 12 articles within this resulting eBook present a series of comprehensive reviews and original research papers on multimodality imaging and targeted radionuclide therapy; illustrating the different facets of studies currently conducted in these domains