succimer and Lymphoma

Cancer targeting nanoprobes with precisely designed physicochemical properties may show enhanced pharmacological targeting and therapeutic efficacy. As a widely used commercialized antibody, rituximab has been in clinical use for three decades and has lengthened or even saved thousands of lives. However, many people cannot benefit from rituximab treatment because of drug resistance or side effects.. Cell targeting experiments and magnetic resonance (MR) signal and T2 measurements showed that the Fe. These results indicate that Fe

Topics: Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Apoptosis; Calcium; Cell Line, Tumor; Cell Survival; Ferric Compounds; Humans; Intracellular Space; Lymphoma; Magnetic Fields; Magnetite Nanoparticles; Membrane Potential, Mitochondrial; Nanopores; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Rituximab; Succimer; Time Factors

Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides. The daughters, especially bismuth-213 (213Bi), tend to accumulate in the kidneys. We tested the efficacy of various pharmacologic agents and the effect of tumor burden in altering the pharmacokinetics of the 225Ac daughters to modify their renal uptake. Pharmacologic treatments in animals were started before i.v. administration of the HuM195-225Ac generator. 225Ac, francium-221 (221Fr), and 213Bi biodistributions were calculated in each animal at different time points after 225Ac generator injection. Oral metal chelation with 2,3-dimercapto-1-propanesulfonic acid (DMPS) or meso-2,3-dimercaptosuccinic acid (DMSA) caused a significant reduction (P < 0.0001) in the renal 213Bi uptake; however, DMPS was more effective than DMSA (P < 0.001). The results with DMPS were also confirmed in a monkey model. The renal 213Bi and 221Fr activities were significantly reduced by furosemide and chlorothiazide treatment (P < 0.0001). The effect on renal 213Bi activity was further enhanced by the combination of DMPS with either chlorothiazide or furosemide (P < 0.0001). Competitive antagonism by bismuth subnitrate moderately reduced the renal uptake of 213Bi. The presence of a higher target-tumor burden significantly prevented the renal 213Bi accumulation (P = 0.003), which was further reduced by DMPS treatment (P < 0.0001). Metal chelation, diuresis with furosemide or chlorothiazide, and competitive metal blockade may be used as adjuvant therapies to modify the renal accumulation of 225Ac daughters.

Topics: Actinium; Alpha Particles; Animals; Antibodies, Monoclonal; Bismuth; Chelating Agents; Female; Francium; Immunotoxins; Kidney; Lymphoma; Macaca fascicularis; Male; Mice; Mice, Inbred BALB C; Mice, SCID; Radioimmunotherapy; Succimer; Unithiol

Thyroid scintigraphy, using 99mTc(V) dimercaptosuccinic acid, was performed in four patients with pathologically confirmed medullary thyroid carcinoma and elevated serum calcitonin values. Significant uptake of the tracer was found in the clinically palpable cervical tumor masses, metastatic sites, and residual tumor. This finding, probably specific for medullary thyroid carcinoma, could be of great use in the diagnosis and the surgical follow-up.

Topics: Adenocarcinoma; Adult; Calcitonin; Carcinoma; Diagnosis, Differential; Female; Humans; Lymphoma; Male; Middle Aged; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms