| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: =99.11%
| Targets |
Somatostatin receptors (SSTRs), specifically high affinity to SSTR2 subtype[1]
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|---|---|
| ln Vitro |
Receptor affinity studies confirmed 177Lu-DOTATATE exhibits enhanced binding to somatostatin receptors compared to octreotide and Tyr³-octreotide, attributed to the structural modification of the peptide analog (Tyr³-octreotate)[16,17].
No additional in vitro assays (e.g., cell proliferation, apoptosis) were described for 177Lu-DOTATATE in this study.[1] |
| ln Vivo |
Excellent anti-tumor effects of 177Lu-DOTATATE have been observed in rats [1].
In Lewis rats bearing dual CA20948 pancreatic tumors (small: ~0.5 cm²; large: 7–9 cm²), a single intravenous injection of 555 MBq 177Lu-DOTATATE (delivering 60 Gy to large tumors) significantly extended survival vs. controls (P<0.001). 25% of animals survived to 150 days post-treatment (equivalent to ~5 human years), though complete remission was not achieved in large tumors due to clonogenic cell burden. In a rat liver micrometastatic model, 177Lu-DOTATATE demonstrated potent antitumor effects, reducing metastatic burden and improving survival. 177Lu-DOTATATE outperformed 90Y-DOTATOC in small tumors (<10 mm diameter), where its medium-energy β-emissions (0.5 MeV) achieved near-complete energy absorption (97% in 10-mm spheres vs. 66% for 90Y).[1] 177Lu-DOTATATE is clinically used for molecular radiotherapy in metastatic neuroblastoma patients selected by 68Ga-DOTATATE PET positivity. It targets SSTR-2-expressing tumors, with clinical efficacy observed in relapsed/refractory pediatric cases. In a Phase IIa trial, 177Lu-DOTATATE demonstrated therapeutic activity in children with primary refractory or relapsed high-risk neuroblastoma, improving disease control.[2] Demonstrated high radiotherapeutic efficacy in a rat tumor model. [3] Compared [177Lu-DOTA0Tyr3]octreotate with [111In-DTPA0]octreotide in patients, showing potential for 177Lu-labelled peptides in peptide receptor radionuclide therapy (PRRT). [3] |
| Enzyme Assay |
In vitro receptor binding assays for DOTATATE are typically performed using membrane preparations extracted from animal tissues (e.g., rat cortex) or tumor cell lines (e.g., AR42J). The general procedure includes: first, radiolabeled DOTATATE (with isotopes such as ¹²⁵I, ⁶⁸Ga, or ¹⁷⁷Lu) is incubated with the membrane preparation in an appropriate buffer. Following incubation, bound and free radioligands are separated by rapid filtration (e.g., using glass fiber filters) or centrifugation, followed by washing with suitable buffer to remove unbound fractions. The radioactivity retained on the filters is measured using a gamma counter to calculate the binding percentage. To determine specific binding and affinity, competition binding experiments are performed by co-incubating the radioligand with various concentrations of unlabeled DOTATATE or other somatostatin analogs (e.g., octreotide), generating competition curves to calculate the half-maximal inhibitory concentration (IC₅₀) or dissociation constant (K_D). Radiochemical purity is typically assessed using High-Performance Liquid Chromatography (HPLC) or Thin-Layer Chromatography (TLC), often on a C18 column with a water-acetonitrile mobile phase containing 0.1% trifluoroacetic acid. For ¹²⁵I-DOTATATE, the maximum binding capacity to membrane preparations is approximately 23%, with an IC₅₀ of about 9 μg/mL.
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| Cell Assay |
In vitro cellular assays for DOTATATE primarily utilize cell lines with high somatostatin receptor subtype 2 (SSTR2) expression, such as AR42J (rat pancreatic acinar cell carcinoma), HEK293 (human embryonic kidney cells stably transfected with SSTR2), or ZR-75-1 (human breast cancer cells). The core experiment is the radioligand uptake and internalization assay: radiolabeled DOTATATE (e.g., ¹⁷⁷Lu-DOTATATE, ⁶⁴Cu-DOTATATE, or ⁵²Mn-DOTATATE) is incubated with cells at 37°C for varying durations (typically 0.5-24 hours). After incubation, cells are washed with an acidic buffer (e.g., 0.1 M glycine-HCl, pH 2.5-3.0) to remove surface-bound radioactivity, then lysed with an alkaline solution (e.g., 1 M NaOH) to determine internalized radioactivity. The internalization rate typically exceeds 50% of total bound activity (e.g., approximately 53% for ⁵²Mn-DOTATATE at 4 hours). To assess specificity, blocking studies are performed by co-incubating with an excess (typically 100-1000 fold) of unlabeled DOTATATE. Cellular uptake kinetics, receptor density (Bmax), and binding affinity (K_D) can be determined through saturation binding experiments or Scatchard analysis. Additionally, colony formation assays can be employed to evaluate the impact of radiolabeled DOTATATE on cell survival.
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| Animal Protocol |
Tumor Model: Male Lewis rats (250–300 g) implanted subcutaneously with CA20948 pancreatic tumor cells. Small (~0.5 cm²) and large (7–9 cm²) tumors were established in contralateral flanks[1]
Dosing: Single intravenous injection via dorsal penile vein: - 177Lu-DOTATATE: 555 MBq (specific activity: 37 MBq/μg peptide) or Fractionated dosing (2 injections, 2 weeks apart): 2 × 278 MBq 177Lu-DOTATATE[1] Endpoint Monitoring: Tumor size (caliper measurements), survival, body weight. Euthanasia criteria: tumor >15 cm² or >10% body weight loss.[1] |
| ADME/Pharmacokinetics |
177Lu-DOTATATE Due to its small peptide chain, it can be rapidly cleared from the blood and remain persistently in SSTR-positive tumors through receptor internalization. Dosimetry assumes a uniform spherical distribution of tumors; the S value is used to calculate the absorbed dose. [1]
Studies have found that the optimal labeling conditions for 177Lu are pH 4-4.5, and the reaction can be completed in 20 minutes at 80°C. [3] High specific activity has been achieved, which is crucial for peptide receptor radionuclide therapy (PRRT). [3] |
| Toxicity/Toxicokinetics |
Clinical data (cited) indicate reversible hematologic toxicity in humans. Dose exposure in adjacent tissues is lower than that in 90Y (e.g., tumor doses in tissues near 131I-like emitters are 4%–46%, compared to 24%–103% in 90Y). [1] Cited clinical studies indicate that the reversible hematologic and renal toxicity profile is consistent with peptide receptor radionuclide therapy (PRRT). [2]
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| References |
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| Additional Infomation |
177Lu-DOTATATE combines therapeutic beta-ray emission (maximum energy 0.5 MeV) and diagnostic gamma-ray emission (energy 113 keV, absorption rate 6.3%), allowing for simultaneous treatment and scintillation monitoring [1].
Clinical efficacy: In patients with gastrointestinal and pancreatic neuroendocrine tumors, 177Lu-DOTATATE achieved a complete/partial response rate of 30% and a minor response rate of 21%. Due to the short range of beta particles (maximum 2.1 mm) and high intratumoral energy absorption rate (e.g., 93% absorption rate in a 5 mm sphere), 177Lu-DOTATATE is best suited for tumors with a diameter of less than 10 mm. [1] 177Lu-DOTATATE is a cornerstone therapy for adult neuroendocrine tumors, improving survival [19]. Its application in pediatric neuroblastoma is emerging. Heterogeneity was observed in SSTR-2 and NAT (norepinephrine transporter) expression: 26 out of 42 neuroblastoma patients showed inconsistent anatomical distributions on 68Ga-DOTATATE (SSTR-2) and 123I-mIBG (NAT) scans. This supports the combined use of 177Lu-DOTATATE and 131I-mIBG to target biologically different tumor clones [2]. Optimal patient selection requires 68Ga-DOTATATE PET/CT scans before treatment to confirm SSTR-2 affinity. [2] Radiolabeling conditions for DOTA peptides: The optimal labeling conditions for 177Lu are pH 4–4.5 and 80°C for 20 minutes, with an incorporation rate of >99% for DOTA-coupled peptides (e.g., DOTATOC, DOTA-tate). The reaction kinetics of 177Lu are faster than those of 90Y or 111In [3]. Maximum achievable specific activity (SA): The theoretical SA is 19 mCi/nmol (Table 1). Experiments show that even at a molar ratio of DOTA peptide to 177Lu as low as 1.2:1, high SA can be obtained. The decay product Hf4+ of 177Lu does not compete with DOTA for binding, thus maintaining a high SA for ≥2 weeks after production [3]. Contaminant interference: The decay products Zr4+ of 90Y and Hf4+ of 177Lu do not inhibit radiolabeling, while the decay product Cd2+ of 111In strongly competes for it (Table 2, Figure 3) [3]. |
| Molecular Formula |
C65H90N14O19S2.XC2H4O2
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|---|---|
| Molecular Weight |
1435.6225
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| Exact Mass |
1436.61
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| Elemental Analysis |
C, 53.80; H, 6.34; N, 13.11; O, 22.46; S, 4.29
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| CAS # |
177943-89-4
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| Related CAS # |
DOTATATE;177943-88-3
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| PubChem CID |
131634410
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| Sequence |
{DOTA}-{d-Phe}-Cys-Tyr-{d-Trp}-Lys-Thr-Cys-Thr (Disulfide bridge:Cys2-Cys7)
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| SequenceShortening |
{DOTA}-{d-Phe}-CY-{d-Trp}-KTCT (Disulfide bridge:Cys2-Cys7)
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
1732.9±65.0 °C at 760 mmHg
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| Flash Point |
1001.8±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.613
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
21
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| Hydrogen Bond Acceptor Count |
34
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
116
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| Complexity |
2740
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| Defined Atom Stereocenter Count |
10
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| SMILES |
NCCCC[C@H](NC([C@H](NC([C@H](CC1=CC=C(O)C=C1)NC([C@H](CS)NC([C@H](NC(CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)=O)CC1=CC=CC=C1)=O)=O)=O)CC1C2=CC=CC=C2NC=1)=O)C(N[C@@H]([C@@H](C)O)C(N[C@@H](CS)C(N[C@@H]([C@@H](C)O)C(O)=O)=O)=O)=O
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| InChi Key |
YHGBTEQKXYHHPW-TWDDAPNHSA-N
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| InChi Code |
InChI=1S/C65H90N14O19S2.4C2H4O2/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66;4*1-2(3)4/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98);4*1H3,(H,3,4)/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+;;;;/m1..../s1
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| Chemical Name |
acetic acid;(2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-[[(2R)-3-phenyl-2-[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]propanoyl]amino]-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoic acid
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| Synonyms |
DOTATATE acetate; DOTA-TATE; Oxodotreotide acetate; Dotatate acetate; DOTA-TATE acetate; 99R86Y6V0M; UNII-99R86Y6V0M; L-Threonine, N-((4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetyl)-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-threonyl-L-cysteinyl-, cyclic (2->7)-disulfide, acetate (salt); 177943-89-4; DOTATATE; DOTA TATE; Dotatate; DOTA-octreotate; DOTAoctreotate; DOTA octreotate;
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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) |
DMSO: 100 mg/mL
H2O: 8.33 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 11.11 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6966 mL | 3.4828 mL | 6.9656 mL | |
| 5 mM | 0.1393 mL | 0.6966 mL | 1.3931 mL | |
| 10 mM | 0.0697 mL | 0.3483 mL | 0.6966 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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