| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
SSTR2 (primary target) and other SSTR subtypes. DOTA-LM3 is a somatostatin receptor antagonist. The DOTA chelator binds radiometals (68Ga, 177Lu), while the LM3 peptide (p-Cl-Phe-cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2) targets SSTRs.
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| ln Vitro |
177Lu-DOTA-LM3 is tolerant. The body, kidneys, spleen, and metastases are the primary locations of 177Lu-DOTA-LM3, which raises the average absorbed dose to organs and tumors [2].
DOTA-LM3 as an unlabeled compound exhibits SSTR antagonism. When radiolabeled with 68Ga or 177Lu, the radiotracer shows favorable biodistribution and higher tumor radiation doses than SSTR agonists in metastatic neuroendocrine neoplasms. The antagonist-based approach provides improved tumor uptake compared to agonist-based PRRT. |
| ln Vivo |
68Ga-DOTA-LM3 shows excellent biodistribution and higher tumor radiation doses compared to SSTR agonists. In preclinical and clinical studies, 68Ga-DOTA-LM3 PET/CT imaging demonstrates superior tumor detection in neuroendocrine tumors (NETs). 177Lu-DOTA-LM3 is being investigated for PRRT of metastatic NETs, with promising tumor uptake and therapeutic efficacy in preclinical models and clinical studies.
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| Enzyme Assay |
Cell-free SSTR binding assays: membranes from CHO-K1 cells expressing human SSTR2 are incubated with [125I]-Tyr11-SRIF-14 (0.1 nM) and increasing concentrations of unlabeled DOTA-LM3 (0.01-10,000 nM) in binding buffer (50 mM HEPES, pH 7.4, 5 mM MgCl2, 0.5% BSA) for 60-90 min at 25degC. Bound radioactivity is separated by GF/B filtration. Ki values are calculated by nonlinear regression. For radiolabeled DOTA-LM3, receptor binding assays are performed using the same method with the labeled compound as the radioligand. For 68Ga- or 177Lu-labeled DOTA-LM3, cells expressing SSTR2 are incubated with the radiolabeled compound to assess specific binding. Binding affinity is determined by displacement with unlabeled SSTR ligands.
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| Cell Assay |
Cell-based binding and internalization assays: HEK293 or CHO-K1 cells overexpressing SSTR2 are incubated with radiolabeled DOTA-LM3 (68Ga- or 177Lu-labeled) at 37degC for 1-4 hours. Cell-bound radioactivity is measured after washing with cold buffer. For internalization studies, cells are washed with acid buffer (pH 2.5) to remove surface-bound radioactivity; internalized radioactivity is measured after cell lysis. In contrast to SSTR agonists, DOTA-LM3 is an antagonist that binds to SSTR2 but does not induce significant internalization. This property may result in higher tumor retention for PRRT by avoiding agonist-induced receptor downregulation.
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| Animal Protocol |
In vivo animal studies are conducted in mice bearing SSTR-positive tumor xenografts (e.g., AR42J rat pancreatic tumor model or human NET xenografts). 68Ga-DOTA-LM3 or 177Lu-DOTA-LM3 is injected intravenously via tail vein (100-200 uL, 5-20 MBq). Mice are imaged by microPET/CT at 0.5, 1, 2, 4, 24 hours post-injection. For biodistribution, mice are sacrificed at time points, and organs (blood, heart, liver, spleen, kidney, pancreas, tumor) are harvested and weighed. Radioactivity is measured using a gamma counter. Tumor-to-background ratios are calculated. 177Lu-DOTA-LM3 therapy studies include multiple injection regimens and tumor growth monitoring.
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| ADME/Pharmacokinetics |
PK properties of radiolabeled DOTA-LM3: The radiopeptide shows rapid blood clearance, primarily renal excretion, and high tumor uptake. 68Ga-DOTA-LM3 has a short plasma half-life (approximately 15-30 min) due to rapid renal elimination. 177Lu-DOTA-LM3 (with longer half-life) shows persistent tumor retention for up to 7-10 days. Biodistribution studies show low accumulation in non-target organs (liver, spleen, bone marrow) and high tumor-to-background ratios, favorable for imaging and therapy.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for unlabeled DOTA-LM3. For radiolabeled DOTA-LM3, toxicity is primarily from radiation exposure (myelosuppression, nephrotoxicity, secondary malignancies). In preclinical studies, 177Lu-DOTA-LM3 is well-tolerated at therapeutic doses, with dose-limiting toxicity being bone marrow suppression (thrombocytopenia, neutropenia) and renal toxicity at higher doses. Clinical PRRT using 177Lu-labeled SSTR antagonists is being evaluated in trials.
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| References |
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| Additional Infomation |
Other information: DOTA-LM3 is a somatostatin receptor antagonist (LM3 peptide conjugated to DOTA chelator). CAS number: 1192362-32-5. The LM3 peptide is p-Cl-Phe-cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2. Radiolabeled versions (68Ga-DOTA-LM3, 177Lu-DOTA-LM3) are used for PRRT and PET imaging of neuroendocrine tumors. The antagonist-based approach offers advantages over agonist-based imaging/therapy, including higher tumor uptake. It is a research agent not FDA-approved for clinical use. For research use only.
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| Molecular Formula |
C69H93CLN16O19S2
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|---|---|
| Molecular Weight |
1550.1555325985
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| Exact Mass |
1548.593
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| CAS # |
1192362-32-5
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| Related CAS # |
DOTA-LM3 TFA
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| PubChem CID |
168355559
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
18
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| Hydrogen Bond Acceptor Count |
26
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| Rotatable Bond Count |
28
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| Heavy Atom Count |
107
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| Complexity |
2910
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C(C1C=CC(=CC=1)NC(=O)N)[C@@H]1C(N[C@H](C(N[C@]([H])(C(N[C@@H](CSSC[C@H](C(N[C@H](C(N1)=O)CC1C=CC(=CC=1)O)=O)NC(=O)[C@@H](NC(=O)CN1CCN(CCN(CCN(CC1)CC(=O)O)CC(=O)O)CC(=O)O)CC1C=CC(=CC=1)Cl)C(=O)N[C@@H](C(=O)N)CC1C=CC(=CC=1)O)=O)[C@H](O)C)=O)CCCCN)=O
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| InChi Key |
KOZHSMBONUANKJ-GPCQATCWSA-N
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| InChi Code |
InChI=1S/C69H93ClN16O19S2/c1-40(87)60-68(104)81-55(66(102)77-50(61(72)97)30-43-9-17-47(88)18-10-43)39-107-106-38-54(67(103)79-53(33-44-11-19-48(89)20-12-44)65(101)78-52(32-42-7-15-46(16-8-42)74-69(73)105)64(100)76-49(62(98)82-60)4-2-3-21-71)80-63(99)51(31-41-5-13-45(70)14-6-41)75-56(90)34-83-22-24-84(35-57(91)92)26-28-86(37-59(95)96)29-27-85(25-23-83)36-58(93)94/h5-20,40,49-55,60,87-89H,2-4,21-39,71H2,1H3,(H2,72,97)(H,75,90)(H,76,100)(H,77,102)(H,78,101)(H,79,103)(H,80,99)(H,81,104)(H,82,98)(H,91,92)(H,93,94)(H,95,96)(H3,73,74,105)/t40-,49+,50-,51+,52-,53+,54-,55+,60+/m1/s1
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| Chemical Name |
2-[4-[2-[[(2S)-1-[[(4R,7S,10S,13R,16S,19S)-10-(4-aminobutyl)-4-[[(2R)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-13-[[4-(carbamoylamino)phenyl]methyl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-3-(4-chlorophenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
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| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6451 mL | 3.2255 mL | 6.4509 mL | |
| 5 mM | 0.1290 mL | 0.6451 mL | 1.2902 mL | |
| 10 mM | 0.0645 mL | 0.3225 mL | 0.6451 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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