succimer and Neoplasm-Metastasis

To investigate the targeting activity of the peptide (named P1c) derived from connective tissue growth factor (CTGF) to αvβ3-rich tumor cells.. P1c was synthesized and conjugated with ultrasuperparamagnetic iron oxide particles (USPIOs) coated with meso-2,3-dimercaptosuccinic acid (DMSA). The specific binding activity of P1c-USPIOs to αvβ3 was verified by solid phase binding assay. The combination of P1c-USPIOs with a human primary liver cancer cell (Bel 7402) with αvβ3-positive expression and uptake of P1c-USPIOs by cells was investigated by Prussian blue staining, transmission electron microscopy (TEM), and magnetic resonance imaging (MRI). The targeting activity of the probe in vivo was also evaluated using a small-animal tumor model by MRI.. The cell uptake of P1c-USPIOs was observed in a dose-dependent manner, whereas no significant particle uptake was found in the plain USPIOs group. The differences on T2*-weighted imaging were also found by MRI and the signal intensity (SI) was statistically reduced after coculture of Bel 7402 cells with P1c-USPIOs at a concentration of 20-80 μg/mL compared with plain USPIOs (P < 0.05). The in vivo study showed that the signal reduction was distributed mainly in the periphery and some central areas of the tumor. The tumor-to-muscle CNR (contrast-to-noise ratio) at 12 hours after the administration of the P1c-USPIOs was statistically significantly different compared to those at 0 hour, 1 hour, or the plain USPIO group (P < 0.05).. The peptide P1c might be a good candidate as a targeting carrier for drugs or tracers.

Topics: Cell Line, Tumor; Coloring Agents; Disease Progression; Ferric Compounds; Ferrocyanides; Humans; Integrin alphaVbeta3; Liver Neoplasms; Magnetic Resonance Imaging; Microscopy, Electron, Transmission; Neoplasm Metastasis; Peptides; Succimer

The aim of this study was to find out if (90)Y could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if (90)Y-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases.. The preparing of (90)Y-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistribution study in healthy male Wistar rats. In vitro stability of the complexes was tested too.. (90)Y-DMSA could be prepared in high yields (>95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that (90)Y-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for (90)Y-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible.. (90)Y complexes could be made with ease with DMSA. (90)Y-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.

Topics: Animals; Bone Neoplasms; Humans; Hydrogen-Ion Concentration; Ligands; Male; Neoplasm Metastasis; Palliative Care; Radionuclide Imaging; Rats; Rats, Wistar; Serum Albumin; Spectrophotometry; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Yttrium

99Tcm-tetrofosmin imaging was performed in 23 thyroid cancer patients and compared with whole-body 131I scans, neck ultrasonography and plasma thyroglobulin levels. Of 22 patients with differentiated thyroid cancer, 8 showed identical images on 131I scan and tetrofosmin; 1 patient with medullary cancer had identical images with 99Tcm-DMSA and 99Tcm-tetrofosmin, the findings being confirmed by sonography. The potential usefulness of 99Tcm-tetrofosmin imaging in the follow-up of thyroid cancers is discussed.

Topics: Biomarkers, Tumor; Follow-Up Studies; Humans; Iodine Radioisotopes; Lymphatic Metastasis; Neoplasm Metastasis; Organophosphorus Compounds; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroglobulin; Thyroid Neoplasms; Ultrasonography

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

Whole body scintigraphy with [99mTc] (v)dimercaptosuccinic acid (pentavalent DMSA) was performed in seven patients with histologically confirmed medullary carcinoma of the thyroid (MCT). Six of these patients had undergone previous thyroid resections for MCT and, although asymptomatic at the time of pentavalent DMSA scintigraphy, had persistent and serial elevations in their plasma calcitonin levels. One additional patient was scanned before and after total thyroidectomy for MCT. The pentavalent DMSA scintigram demonstrated either local neck recurrence (three patients) or distant metastases (two patients) in five of the six asymptomatic patients. In one asymptomatic patient only equivocal neck uptake was demonstrated. Since he had only minimal calcitonin elevations, repeat neck exploration was not performed. The one patient studied before thyroid resection for MCT demonstrated neck uptake before, but not after, total thyroidectomy. The results of the scintigrams had significant impact on patient care and resulted in neck re-exploration (three patients), neck biopsy (one patient), and lumbar spine biopsy and subsequent radiotherapy (one patient). These data demonstrate pentavalent DMSA to be a sensitive localizing agent in the evaluation of asymptomatic MCT patients with hypercalcitonaemia. Accurate targeting of treatment may be shown in due course to have a beneficial impact on survival.

Topics: Adult; Calcitonin; Carcinoma; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organotechnetium Compounds; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms; Thyroidectomy

99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12 (80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of 99mTc(V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of 99mTc(V)-DMSA (64.9%). In addition, 99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of 99mTc(V)-DMSA concentration in soft tissue and bone metastasis was similar.

Topics: Adult; Carcinoma; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Radionuclide Imaging; Reagent Kits, Diagnostic; Succimer; Sulfhydryl Compounds; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Bone Neoplasms; Carcinoma; Evaluation Studies as Topic; Humans; Iodine Radioisotopes; Iodobenzenes; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organometallic Compounds; Radionuclide Imaging; Soft Tissue Neoplasms; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Thyroid Neoplasms

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Child, Preschool; Drug Evaluation; Female; Gallium Radioisotopes; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid

Topics: Carcinoma, Bronchogenic; Humans; Kidney Cortex; Kidney Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium