Evaluation of Tc-99m (V) DMSA Binding to Human Plasma Proteins (original) (raw)
Related papers
Dimercaptosuccinic acid: A multifunctional cost effective agent for imaging and therapy
Indian Journal of Nuclear Medicine, 2015
the renal parenchyma. Two main Tc-99m DMSA tubular uptake routes have been proposed (i) peritubular extraction from plasma and (ii) tubular reabsorption. [5,6] Muller and Gutsche in 1995 proposed that after injection, Tc-99m DMSA is bound to plasma proteins in the circulating blood and penetrate the glomerular filter at very low rates. Tc-99m DMSA is completely excreted and does not reabsorbed from the tubular fluid. Peritubular excretion accounts for the Tc-99m DMSA uptake in the proximal tubular cells of the renal cortex. Tc-99m DMSA is then bound to the cell plasma protein with a high binding constant and accumulates in the kidney. [6] Burckhardt et al. proposed the role of sodium-dependent dicarboxylate transporter (NaDC-3) in the basolateral uptake of Tc-99m DMSA from peritubular capillaries into proximal tubule cells. [7] Tc-99m DMSA reabsorption from the glomerular ultra-filtrate substantially contributes to the renal uptake of the tracer. [8-10] Recently, Weyer et al. studied the role of the megalin/cubilin receptors for the accumulation of Tc-99m DMSA and proposed that Tc-99m DMSA binds to α-1 microglobulin plasma protein. Tc-99m DMSA is freely filtered by glomeruli and accumulates in renal proximal tubules by multiligand-binding mediated by megalin/cubilin receptor endocytosis. Free Tc-99m DMSA and trace amounts of microglobulin-bound Tc-99m DMSA are excreted in the urine. [11] Pentavalent Tc-99m (V) dimercaptosuccinic acid Tc-99m (V) DMSA localizes in a number of tumor types, most notably medullary thyroid carcinoma (MTC), bone metastases and other bone lesions. At pentavalent state, both sulfhydryl groups (-SH) of DMSA are bound with Tc-99m and no free-SH group is left for protein binding [Figure 1b]. The small Tc-99m (V) DMSA complex does not accumulate in the kidney and gets easily excreted by the kidney.
99mTc-Labeled Tricarbonyl His-CNA35 as an Imaging Agent for the Detection of Tumor Vasculature
Journal of Nuclear Medicine, 2012
Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. Methods: 99m Tc-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. 99m Tc-(CO) 3 His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. Results: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. 99m Tc-(CO) 3 His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of 99m Tc-(CO) 3 His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. Conclusion: 99m Tc-(CO) 3 His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.
Nuclear Medicine and Biology, 2007
We report here the results of studies on the in vitro receptor binding affinity, in vivo tumor uptake and biodistribution of two ""re labeled peptides. Methods: Peptides P587 and P829 were synthe sized by N-a-Fmoc peptide chemistry, purified by reversed-phase HPLC and characterized by fast-atom bombardment mass spectrometry. The peptides were labeled with 99mTcby ligand exchange from 99mTc-glucoheptonate. In vitro somatostatin receptors (SSTR)binding affinities of P587, P829 and their oxorhenium complexes, [DTPAJoctreotide and ln-[DTPA]octreotide were determined in an inhibition assay using AR42J rat pancreatic tumor cell membranes and 125l-[Tyr3]somatostatin-14 as the probe. In vivo single-and dual-tracer studies of ""Tc peptides and 111ln-[DTPA]octreotide were carried out using Lewis rats bearing CA20948 rat pancreatic tumor implants. Results: Technetium-99m-P587 and 99rrTc-P829 of high-specific activity (>60 Ci (2.2 TBq)/mmole) were prepared in >90% radiochemical yield. P587 and P829 had a Ki = 2.5 n/Wand 10 n/W, respectively.
Applied Radiation and Isotopes, 2006
This study describes the radiolabeling and preliminary biologic testing of diethylenetriaminepentaacetic acid (DTPA)-deoxyglucose (DG) labeled with 99m Tc. A one-step [ 99m Tc]-DTPA-DG kit was prepared using the stannous chloride reduction method. When 99m TcO 4 À was added to the DTPA-DG kit at room temperature the radiochemical purity 30 min later was 99.2%, and it remained 498.6% for 6 h. Rapid blood clearance of [ 99m Tc]-DTPA-DG was observed in in vivo biodistribution, the main route of clearance was via the kidneys. No significant accumulation in any other organs was seen. The tumor-to-brain and tumor-to-muscle concentration ratios for [ 99m Tc]-DTPA-DG uptake were higher than those for fluorine-18-flurodeoxyglucose ( 18 F-FDG). Scintigraphic results demonstrated the feasibility of [ 99m Tc]-DTPA-DG imaging tumors. The [ 99m Tc]-DTPA-DG complex is a potential imaging agent due to the ideal physical characteristics of the radionuclide, ease of preparation, low cost, early accumulation and the preference for the renal route of excretion. r
Cancer Biotherapy and Radiopharmaceuticals, 2012
Background: The currently available radiopharmaceuticals are not specific for tumor imaging. Purpose: The present study was conducted to radiolabel doxorubicin with Technetium-99m ([99m]Tc) as a scintigraphic marker of high DNA turnover/intercalation in malignant cells. Methods: Labeling was done by direct method and the developed radiotracer was subjected to quality control tests. The blood kinetics, scintigraphy of tumor-bearing mice, and biodistribution were studied after intravenous injection of about 7.4 MBq of [99m]Tc-doxorubicin. The isotime (5 minutes) anterior images were acquired at different time intervals of 1.5, 3, and 4 hours. Results: The labeling efficiency of [99m]Tc-doxorubicin was estimated to be more than 95%. The protein-binding efficiency was greater than 88% and in vitro stability was up to 24 hours. The biodistribution data support the clearance of the radioligand by dual (renal and hepatic) pathways. A semiquantitative data analysis of the anterior images indicated that a focal concentration of the radiotracer was seen in the tumor at 1.5 hours, which persisted in 3-hour and 4-hour images, respectively. Conclusions: This scintigraphic approach, therefore, could be a powerful tool for cancer detection at early stage. The technique, however, needs further validation through animal experimentation and clinical studies.
Complex ([99mTc]-TA-DG) As a Tumor Imaging Agent
2016
Introduction: This report describes the synthesis of 2-Amino-2-deoxy(S-benzoylthioacetyl)-D-glucose (S-Bz-TA-DG), radiolabeled with [ 99m Tc(CO) 3 (OH 2) 3 ] + complex with a procedure including deprotection of the benzoyl group, characterization by HPLC using a C18 reverse phase column and preliminary biodistribution study in normal mice. Methods: [ 99m Tc(CO) 3 (H 2 O) 3 ] + complex was used to label TA-DG with 99m Tc. This complex was prepared using up to 46 mCi of Na 99m TcO 4 in 1mL saline. The radiochemical purity (>95%) was determined by TLC in normal saline solution as the mobile phase. Radio-HPLC analysis of [ 99m Tc]-(TA-DG) at pH=9.5-10, revealed that labeling with 99m Tc resulted in the formation of three radiochemical species (Na 99m TcO 4 with t R =5.7 min, [ 99m Tc(CO) 3 (H 2 O) 3 ] + complex with t R =27.5 min and [ 99m Tc]-(TA-DG) [yield >85%] with t R =8.2 min) with different HPLC-profiles. Results:. The biodistribution of the [ 99m Tc]-(TA-DG) complex was studied in normal mice (body mass 25-35 g) at 30 min and 1 h post-injection, according to a published procedure. This complex showed negligible brain uptake (0.13%±0.03 ID) at 30 min post-injection, an efficient clearance from the blood, a rapid excretion to the urine and a low retention in the liver and kidneys. Conclusion: Nonfunctionalized carbohydrate compounds such as glucose are generally weak ligands for chelating with 99m Tc. Therefore, functionalization with an external chelating group or the insertion of some functional groups is essential to obtain strong metal-binding compounds. On the basis of our results, it seems that [ 99m Tc]-(TA-DG) has not most of the favorable properties as an imaging agent for brain tumors.
During the past decade, several peptides containing Arg-Gly-Asp sequence have been conjugated with different chelating agents for labeling with various radionuclides for the diagnosis of tumor development. In this study, we report the synthesis of two tetrapeptides (Asp-Gly-Arg-His and Asp-Gly-Arg-Cys) and one hexapeptide [Asp-Gly-Arg-D-Tyr-Lys-His] by changing the amino acid sequence of the Arg-Gly-Asp motif. Peptide synthesis was initiated from aspartic acid. Aspartic acid placed at C-terminal end of the peptide chain can be conjugated with different drug molecules facilitating their transport to the site of action. The peptides were synthesized in excellent yield and labeled using freshly prepared [ 99m Tc(CO) 3 (H 2 O) 3 ] + intermediate. A complexation yield of over 97% was achieved under mild conditions even at low ligand concentrations of 10 À2 M. Radiolabeled peptides were characterized by HPLC and were found to be substantially stable in saline, in His solution as well as in rat serum and tissue (kidney, liver) homogenates. Internalization studies using Ehrlich ascites carcinoma cell line showed rapid and significant internalization (30-35% at 30 min of incubation attaining maximum value of about 40-60% after 2-4 h incubation). A good percentage of quick internalization was also observed in a v b 3 -receptor-positive B16F10 mouse melanoma cell line (14-16% after 30 min of incubation and 25-30% after 2-4 h incubation). Imaging and biodistribution studies were performed in Swiss albino mice bearing Ehrlich ascites tumor in right thigh. Radiolabeled peptides exhibited fast blood clearance and rapid elimination through the urinary systems. 99m Tc(CO) 3 -tetra-Pep2 exhibited remarkable localization at tumor site (1.15%, 1.17%, and 1.37% ID/g at 2, 4, and 6 h p.i., respectively) which could be due to slow clearance of the radiolabeled peptide from blood in comparison with the other two radiolabeled peptides. However, 99m Tc(CO) 3 -hexa-Pep exhibited the highest tumor to muscle and tumor to blood ratios among the three. The preliminary results with these amino acid-based peptides are encouraging enough to carry out further experiments for targeting tumor.