succimer and Multiple-Myeloma

Cancer stem cells (CSCs) are thought to be responsible for the relapse of multiple myeloma (MM). The objective of this study was to target therapy of MM cancer stem cells using gamma-Fe2O3@DMSA magnetic nanoparticle combination with paclitaxel and anti-ABCG2 monoclonal antibody, and to evaluate the combined therapeutic efficacy. CSCs were isolated from human MM cell line RPMI 8226 based on negative expression of CD138 and CD34. In vivo and in vitro studies demonstrated that the isolated CD138-CD34- cells displayed certain stem cell characteristics, including significant increase in expression of ABCG2 transporter, proliferation, mobility, drug resistance, clonogenic potential in soft agar media and tumorigenecity in mice. Treatment with nanoparticles, paclitaxel and anti-ABCG2 antibody remarkably inhibited the growth of CD138-CD34- cells in vitro and their derived tumors in xenografts. The inhibition was also correlated with elevated expression of caspase-9, caspase-8 and caspase-3, and down-regulation of NF-KB. Our data indicate that the nanoparticle combination with paclitaxel and anti-ABCG2 monoclonal antibody offers an effective approach to treatment of MM CSCs through an apoptotic pathway.

Topics: Animals; Antibodies, Monoclonal; Apoptosis; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Caspases; Cell Line, Tumor; Cell Movement; Cell Survival; Disease Models, Animal; Humans; Magnetite Nanoparticles; Mice; Multiple Myeloma; Neoplasm Proteins; Neoplastic Stem Cells; NF-kappa B; Paclitaxel; Particle Size; Signal Transduction; Succimer; Tumor Burden

The objective of this study was to compare the uptake changes of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) and Tc-99m pentavalent dimercaptosuccinic acid (V-DMSA) in multiple myeloma (MM) lesions in response to high-dose chemotherapy (HDC).. The authors compared Tc-99m MIBI and Tc-99m V-DMSA scans before and after HDC in a patient with focal MM lesions without amyloidosis who had received previous standard chemotherapy as well.. HDC had the effect of eliminating all Tc-99m MIBI uptake in the lesions. Tc-99m V-DMSA uptake was increased in lesions presenting significant initial Tc-99m MIBI uptake. In 1 particular lesion that demonstrated this phenomenon, magnetic resonance showed necrosis of the area of MM.. The authors consider that the effect of increasing Tc-99m V-DMSA uptake in the absence of an increase in viable plasma cells possibly reflects the treatment-generated inflammatory and fibrotic changes and not necessarily viable tumor tissue. Exclusive focal Tc-99m V-DMSA uptake in this clinical setting could be considered as a sign of effectively treated lesions and not a sign of deterioration.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dexamethasone; Doxorubicin; Humans; Male; Multiple Myeloma; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Skull; Succimer; Technetium Tc 99m Sestamibi; Tibia; Treatment Outcome; Vincristine

The authors present a patient with Fanconi syndrome who demonstrated poor renal uptake of Tc-99m DMSA and high urinary concentration of the tracer. Tc-99m DTPA imaging was normal and the creatinine clearance was only minimally decreased. These findings suggest that Tc-99m DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption. A Tc-99m MDP bone scan showed faint renal uptake, as well as diffuse high skeletal uptake, particularly in the spine, demonstrating that the metabolic bone disease associated with Fanconi syndrome can be one of the causes of poor renal visualization on a bone scan.

Topics: Bone and Bones; Fanconi Syndrome; Female; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Multiple Myeloma; Organotechnetium Compounds; Radioisotope Renography; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Technetium Tc 99m Medronate

Topics: Aged; Aged, 80 and over; Amyloidosis; Cardiomyopathies; Heart; Humans; Male; Multiple Myeloma; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

A pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scan was performed on a patient with multiple myeloma without amyloidosis. A high accumulation of the tracer was found in numerous tumors. We believe that the accumulation of DMSA is unrelated to amyloidosis and that the DMSA scan may have potential for the staging of tumors in patients presenting with multiple myeloma.

Topics: Bone Neoplasms; Female; Humans; Middle Aged; Multiple Myeloma; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Technetium Tc 99m Medronate