succimer and Neoplasms

This review summarizes and comments on current knowledge in dermatomyositis.. The 2018 European Neuromuscular Centre classification of dermatomyositis has been challenging by the discovery of clinicopathological features associated with dermatomyositis-specific antibody (DMSA) that were not incorporated in the original criteria. These features include but may not be limited to the presence of perifascicular necrosis in anti-Mi-2 dermatomyositis; presence of diffuse nonperifascicular sarcoplasmic myxovirus resistance protein A expression in anti-MDA5 dermatomyositis; and dermatomyositis sine dermatitis in anti-NXP-2 dermatomyositis. Variations and subclassifications within the same DMSA subtypes are observed: anti-MDA5 dermatomyositis is clinically subcategorized into good, intermediate, and poor prognostic subgroups; concurrent anti-CCAR1 and anti-TIF1-γ positivity identify anti-TIF1-γ-positive patient with a lower risk for cancer-associated myositis. Owing to distinct IFN1-signaling pathway activation in dermatomyositis, JAK-STAT inhibitor - the pathway-targeted therapy, have been studied with promising results in refractory dermatomyositis and some new-onset dermatomyositis. In addition, the potential serum biomarkers for IFN1 pathway activation are being investigated for their performance in monitoring the disease activity and the efficacy of the treatment.. DMSA, evidence of prominent IFN1 pathway activation, and risk/severity-associated biomarkers would likely play major roles in future dermatomyositis classification, disease monitoring, and treatment decision.

Topics: Autoantibodies; Biomarkers; Dermatomyositis; Humans; Myositis; Neoplasms; Succimer

Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting β(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.

Topics: Adsorption; Antibodies, Monoclonal; Arthritis, Rheumatoid; Bone Neoplasms; Carcinoma, Hepatocellular; Chromatography; Coronary Disease; Drug Combinations; Equipment Design; Humans; Iodized Oil; Liver Neoplasms; Musculoskeletal Pain; Neoplasms; Organometallic Compounds; Palliative Care; Peptides; Radioimmunotherapy; Radioisotopes; Radionuclide Generators; Radiopharmaceuticals; Rhenium; Skin Neoplasms; Succimer

The most commonly used radionuclides for cancer patients in Japan have been still 67Ga and 201T1 chloride. In addition to the diagnosis of lung cancer and thyroid tumor, 201T1 is recently applied to patients with brain tumor, bone and soft tissue tumor and parathynoid adenoma. Comparing to Nuclear Cardiology and Brain Nuclear Medicine, where many new radiopharmaceuticals have been developed, there are few new drugs in Nuclear Oncology. In other words, new radiopharmaceuticals are expected to be developed for the diagnosis and/or therapy of cancer. In addition to 131I for thyroid cancer, new radiopharmaceuticals such as 111In-octreotide and 99mTc(V)-DMSA have been clinically employed. In spite of strong expectation, radiolabeled monoclonal antibodies have not been clinically used in Japan. However, the technique of humanized antibodies has been established and in U.S.A., 131I-labeled antibodies are reported to be effective for the treatment of malignant lymphoma. 89Sr is useful for the relief of bone pain caused by the bone metastasis. New findings that SPECT of 18F-FDG, a positron emitter, has been revealed to have a great potential in the management of cancer patients, will give a great impact on Nuclear Oncology.

Topics: Gallium Radioisotopes; Humans; Neoplasms; Organotechnetium Compounds; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

Angiogenesis is an essential process for tumor progression. Tumor vasculature-targeting peptides have shown great potential for use in cancer imaging and therapy. Our previous studies have shown that GEBP11, a novel vasculature-specific binding peptide that exhibits high affinity and specificity to tumor angiogenesis, is a promising candidate for the diagnosis and targeted radiotherapy of gastric cancer. In the present study, we developed a novel magnetic resonance and fluorescence (MR/Fluo) dual-modality imaging probe by covalently coupling 2,3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and Cy5.5 to the GEBP11 peptide. The probe Cy5.5-GEBP11-DMSA-MNPs (CGD-MNPs), with a hydrodynamic diameter of 82.8 ± 6.5 nm, exhibited good imaging properties, high stability and little cytotoxicity. In vivo MR/Fluo imaging revealed that CGD-MNPs were successfully applied to visualize tumor angiogenesis in SGC-7901 xenograft mouse models. Prussian blue and CD31 immunohistochemical staining confirmed that CGD-MNPs co-localized with tumor blood vessels. In conclusion, CGD-MNPs are promising candidates for use as MR and fluorescence imaging probes for visualizing gastric cancer angiogenesis in vivo.

Topics: Animals; Carbocyanines; Cell Death; Diagnostic Imaging; Endocytosis; Fluorescence; Human Umbilical Vein Endothelial Cells; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetite Nanoparticles; Mice, Nude; Neoplasms; Neovascularization, Pathologic; Peptides; Rats; Succimer; Tissue Distribution

Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment.

Topics: 3T3 Cells; Animals; Antineoplastic Agents; Apoptosis; Cell Survival; Cells, Cultured; CHO Cells; Comet Assay; Cricetinae; Cricetulus; Humans; Lymphocytes; Magnetic Phenomena; Magnetite Nanoparticles; MCF-7 Cells; Mice; Neoplasms; Nitrosation; Sodium Nitrite; Succimer; Thiomalates

As radio- and chemotherapy-based cancer treatments affect both tumors and healthy tissue, cancer immunotherapy attempts to specifically enhance the natural immune response to tumor cells. In mouse models of cancer, we tested uniform dimercaptosuccinic acid (DMSA)-coated monodisperse magnetic nanoparticles as a delivery system for the anti-tumorigenic cytokine IFN-γ. IFN-γ-adsorbed DMSA-coated magnetic nanoparticles were targeted to the tumor site by application of an external magnetic field. We analyzed nanoparticle biodistribution before and after IFN-γ conjugation, as well as the efficiency of nanoparticle accumulation in tumors, IFN-γ release in the area of interest, and the effects of both on tumor development. At the tumor site, we observed a high degree of nanoparticle accumulation and of cytokine delivery, which led to increased T cell and macrophage infiltration and promoted an anti-angiogenic effect. The combined action led to a notable reduction in tumor size. Our findings indicate that IFN-γ-adsorbed DMSA-coated magnetite nanoparticles can be used as an efficient in vivo drug delivery system for tumor immunotherapy.

Topics: Animals; Cell Line, Tumor; Cell Survival; Female; Immunotherapy; Interferon-gamma; Magnetite Nanoparticles; Mice; Mice, Inbred C57BL; Neoplasms; Succimer

Quantitative 99mTc-dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute 99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between 99mTc-DMSA uptake and cumulative ifosfamide dose was found (P < 0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. 99mTc-DMSA uptake was more consistent than beta 2-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. 99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced 99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that 99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Ifosfamide; Infant; Kidney Diseases; Kidney Tubules; Male; Neoplasms; Organotechnetium Compounds; Radioisotope Renography; Sensitivity and Specificity; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

A kit has been developed to instantly prepare 99mTc(V)-DMSA. The freeze-dried kit consisting of DMSA, stannous chloride and ascorbic acid in appropriate proportions, produces quality 99mTc(V)-DMSA when mixed with 0.2 mL of 3.5% NaHCO3 solution and 2-4 mL of (99mTc)pertechnetate. The radiopharmaceutical characterized by chromatography with ITLC-SG in 0.9% saline and horizontal paper electrophoresis in 50 mM vernol buffer, pH 8.6, at a potential gradient of 15 V/cm showed a different mobility with respect to 99mTc(III)-DMSA, a known agent for kidney imaging. The new agent exhibited less plasma protein binding compared to that of 99mTc(III)-DMSA. Biodistribution of the pentavalent DMSA in mouse demonstrated greater uptake in bone and muscle and lower uptake in liver and kidney with respect to trivalent DMSA. The soft tissue tumour specificity and its suitability for tumour scintigraphy was apparent from the scintigrams of mammary carcinoma in a C3H Jax mouse and medullary carcinoma in a patient. Brain metastatic lesions were also visible in a breast carcinoma patient after administering him with the agent.

Topics: Animals; Blood Proteins; Humans; Mice; Neoplasm Metastasis; Neoplasms; Organotechnetium Compounds; Protein Binding; Rabbits; Radionuclide Imaging; Reagent Kits, Diagnostic; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Tissue Distribution

[186Re]Re(V)DMSA, a beta-emitting analogue of the tumour imaging radiopharmaceutical pentavalent [99mTc]Tc(V)DMSA of possible value in tumour therapy, is readily prepared by stannous reduction of [186Re]ReO4 in the presence of dimercaptosuccinic acid at 100 degrees C using a commercial DMSA kit as used for renal imaging with 99mTc, and purified using a disposable sample preparation column. The complex has been identified as [ReO(DMSA)2] by NMR, optical and i.r., spectroscopy and elemental analysis.

Topics: Humans; Indicators and Reagents; Isomerism; Molecular Structure; Neoplasms; Organometallic Compounds; Radioisotopes; Rhenium; Succimer

Topics: Humans; Neoplasms; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

Sixty patients with a variety of malignant tumors were examined with Tc-99m(V) dimercaptosuccinic acid (DMSA) prepared by modification of a commercially available DMSA kit. Significant uptake of Tc-99m(V)-DMSA was observed in a number of tumors, offering additional clinically useful information. In the majority of cases in this study, however, the benefit of the Tc-99m(V)-DMSA image was limited because of low sensitivity. The most striking observation was the similarity between the tumor concentration of Tc-99m(V)-DMSA and the Tc-99m-MDP uptake in the tumor on the regular bone image. Therefore, patients with Tc-99m-MDP uptake in nonosseous tumor sites on the bone scan may be suitable candidates for tumor imaging with Tc-99m(V)-DMSA.

Topics: Bone and Bones; Evaluation Studies as Topic; Humans; Neoplasms; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Technetium Tc 99m Medronate

Considering the favourable nuclear properties of 99Tcm over 67Ga, we have developed a new tumour-seeking agent, 99Tc(V)m dimercaptosuccinic acid (Tc(V)-DMSA). In order to evaluate the clinical usefulness of Tc(V)-DMSA scintigraphies, 492 patients were studied with Tc(V)-DMSA, and in some cases, where possible, the results were compared with conventional 67Ga citrate scintigraphies. There was a high degree of usefulness of Tc(V)-DMSA in patients with head and neck tumours, medullary thyroid carcinomas and soft tissue tumours. But in patients with carcinomas of the lung, liver and gastrointestinal tract, malignant melanoma and lymphoma, Tc(V)-DMSA was of no or little use.

Topics: Drug Evaluation; Gallium Radioisotopes; Head and Neck Neoplasms; Humans; Neoplasms; Organometallic Compounds; Radionuclide Imaging; Soft Tissue Neoplasms; Succimer; Sulfhydryl Compounds; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

Topics: Humans; Isotope Labeling; Neoplasms; Organometallic Compounds; Radionuclide Imaging; Reagent Kits, Diagnostic; Succimer; Sulfhydryl Compounds; Technetium Tc 99m Dimercaptosuccinic Acid

Being aware of the ideal nuclear properties of Tc-99m, our interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studies with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.

Topics: Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasms; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid

Topics: Gallium Radioisotopes; Head and Neck Neoplasms; Humans; Neoplasms; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid