| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Chelating agent
The compound itself does not have a biological target but serves as a linker to deliver radionuclides to biological targets. Its function is to chelate metal ions (such as Lu(III), Gd(III), In(III), Y(III), and Cu(II)) and covalently attach to antibodies or other proteins via the isothiocyanate group. |
|---|---|
| ln Vitro |
Five distinct metal ions are complexed with p-SCN-Bn-DOTA: In(III), Y(III), Lu(III), Gd(III), and Cu(II)[2].
Nimotuzumab conjugates were obtained with high purity. Radiolabeling yield and specific activities ranged from 63.6% to 94.5% and from 748 to 1142 MBq/mg, respectively. The stability in DTPA excess and human serum was 95.9% and 93.2% after 10 days, respectively. The radioimmunoconjugate showed specific receptor binding in tumor cell lines. [1] In vitro, p-SCN-Bn-DOTA forms stable complexes with various metal ions, including Lu(III), Gd(III), In(III), Y(III), and Cu(II). Its chelation efficiency and stability are assessed by incubating it with the metal ion of interest and measuring the complex formation using techniques like HPLC or mass spectrometry. |
| ln Vivo |
Biodistribution in healthy animals showed the typical behavior of the immunoconjugates based on monoclonal antibodies. The study in xenografts mice demonstrated uptake of (177)Lu-Nimotuzumab in the tumor and reticuloendothelial organs.
Conclusions: (177)Lu-Nimotuzumab was obtained with high purity and specific activities under optimal conditions without significant loss in immunoreactivity and might be a potential radioimmunoconjugate for radioimmunotherapy of tumors with epidermal growth factor receptor overexpression. [1]
Specific in vivo activity is not applicable to the chelator itself. Its utility is demonstrated in vivo when conjugated to a targeting antibody and labeled with a radionuclide. The resulting radiolabeled conjugate is then used for targeted imaging (e.g., PET, SPECT) or therapy, where it binds to tumor-specific antigens and delivers the radioactive payload. |
| Enzyme Assay |
Nimotuzumab was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), testing different molar ratios. The immunoconjugates were characterized. The radiolabeling with (177)Lu was optimized. Radioimmunoconjugates stability was tested in 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid (DTPA) excess and human serum. In vitro studies were performed in tumor model cell lines. Receptor-specific binding was tested by competitive inhibition.[1]
Tenatumomab is an anti-tenascin murine monoclonal antibody previously used in clinical trials for delivering radionuclides to tumors by both pre-targeting (biotinylated Tenatumomab within PAGRIT) and direct 131Iodine labeling approaches. Here we present the synthesis and in vitro characterization of three Tenatumomab conjugates to bifunctional chelating agents (NHS-DOTA, NCS-DOTA and NCS-DTPA). Results indicate ST8198AA1 (Tenatumomab-DOTAMA, derived by conjugation of NHS-DOTA), as the most promising candidate in terms of conjugation rate and yield, stability, antigen immunoreactivity and affinity. Labeling efficiency of the different chelators was investigated with a panel of cold metals indicating DOTAMA as the best chelator. Labeling of Tenatumomab-DOTAMA was then optimized with several metals and stability performed confirms suitability of this conjugate for further development. ST8198AA1 represents an improvement of the previous antibody forms because the labeling with radionuclides like 177Lu or 64Cu would allow theranostic applications in patients bearing tenascin expressing tumors. [2] To conjugate p-SCN-Bn-DOTA to an antibody, the antibody is first prepared in a suitable buffer (e.g., carbonate buffer, pH 9.0). The p-SCN-Bn-DOTA is added, and the mixture is incubated. The reaction involves the nucleophilic attack of the antibody's lysine residues on the isothiocyanate group, forming a stable thiourea bond. The conjugated antibody is then purified from excess chelator. |
| Cell Assay |
To chelate a metal ion, the DOTA-antibody conjugate is incubated with the metal ion (e.g., 177Lu) in an appropriate buffer (e.g., ammonium acetate, pH 5.5-6.0) at elevated temperature. The radiolabeling efficiency and stability of the complex are assessed using instant thin-layer chromatography (ITLC) or size-exclusion HPLC.
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| Animal Protocol |
(177)Lu-Nimotuzumab in vivo studies were conducted in healthy and xenograft animals.
The in vivo performance of the p-SCN-Bn-DOTA-based conjugate is evaluated in animal models, typically mice bearing xenograft tumors. The radiolabeled antibody is administered intravenously, and its biodistribution is determined by measuring radioactivity in various tissues at different time points. Imaging studies (e.g., SPECT/CT or PET/CT) are performed to visualize tumor targeting. |
| ADME/Pharmacokinetics |
Pharmacokinetic data are primarily associated with the final antibody-chelator-radionuclide conjugate, not the chelator alone. The chelator's properties influence the stability and clearance of the metal complex in vivo. The compound is a solid and is typically stored at -20°C.
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| Toxicity/Toxicokinetics |
Toxicity is primarily associated with the metal ion being chelated and the antibody component, rather than the p-SCN-Bn-DOTA itself. The chelator is designed to tightly bind metals to prevent their release and subsequent toxicity. Standard safety precautions for handling chemicals should be observed.
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| References |
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| Additional Infomation |
The humanized monoclonal antibody nimotuzumab (h-R3) has shown superior clinical efficacy compared to other monoclonal antibodies in the immunotherapy of tumors overexpressing epidermal growth factor receptor. This study aimed to prepare and optimize the radiolabeling of (177)Lu-nimotuzumab and to conduct its preclinical evaluation. [1]
p-SCN-Bn-DOTA is a critical component in the field of nuclear medicine and targeted therapy. Its ability to stably bind a wide range of radionuclides and conjugate to biological molecules makes it a versatile tool for developing radiopharmaceuticals. It is used in the preparation of agents for radio-guided surgery, radioimmunoassay, and tumor therapy. |
| Molecular Formula |
C24H33N5O8S
|
|---|---|
| Molecular Weight |
551.61
|
| Exact Mass |
551.205
|
| CAS # |
127985-74-4
|
| PubChem CID |
10123265
|
| Appearance |
White to off-white solid powder
|
| LogP |
-7.2
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
38
|
| Complexity |
863
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CN(CCN(C(CN(CCN1CC(=O)O)CC(=O)O)CC2=CC=C(C=C2)N=C=S)CC(=O)O)CC(=O)O
|
| InChi Key |
UDOPJKHABYSVIX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H33N5O8S/c30-21(31)13-26-5-6-27(14-22(32)33)9-10-29(16-24(36)37)20(12-28(8-7-26)15-23(34)35)11-18-1-3-19(4-2-18)25-17-38/h1-4,20H,5-16H2,(H,30,31)(H,32,33)(H,34,35)(H,36,37)
|
| Chemical Name |
2-[4,7,10-tris(carboxymethyl)-6-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
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| Synonyms |
127985-74-4; p-SCN-Bn-DOTA; (p-SCN-Bn)-dota; p-SCN-Bz-dota; 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraaceticacid, 2-[(4-isothiocyanatophenyl)methyl]-; UNII-13KT123BYW; 13KT123BYW; 2-[4,7,10-tris(carboxymethyl)-6-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid;
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 20.83 mg/mL (37.76 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8129 mL | 9.0644 mL | 18.1288 mL | |
| 5 mM | 0.3626 mL | 1.8129 mL | 3.6258 mL | |
| 10 mM | 0.1813 mL | 0.9064 mL | 1.8129 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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