DOTA-TATE

Short description: Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE

Names
Other names

DOTA-(Tyr3)-octreotate

Identifiers

CAS Number

* 177943-89-4 Y

3D model (JSmol)

* Interactive image

ChemSpider |

* 9345959

PubChem CID

* 11170867

UNII |

* 99R86Y6V0M Y

InChI

* InChI=1S/C65H90N14O19S2/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/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)/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+/m1/s1

Key: QVFLVLMYXXNJDT-CSBVGUNJSA-N

* InChI=1/C65H90N14O19S2/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/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)/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+/m1/s1

Key: QVFLVLMYXXNJDT-CSBVGUNJBN

SMILES

* C[C@H]([C@H]1C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N1)CCCCN)CC2=CNC3=CC=CC=C32)CC4=CC=C(C=C4)O)NC(=O)[C@@H](CC5=CC=CC=C5)NC(=O)CN6CCN(CCN(CCN(CC6)CC(=O)O)CC(=O)O)CC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)O

Properties

Chemical formula

| C65H90N14O19S2
Molar mass | 1435.63 g·mol−1

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

DOTA-TATE (DOTATATE,[1] DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate,[2] and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

DOTA-TATE can be reacted with the radionuclides gallium-68 (T1/2 = 68 min), lutetium-177 (T1/2 = 6.65 d) and copper-64 (T1/2 = 12.7 h) to form radiopharmaceuticals for positron emission tomography (PET) imaging or radionuclide therapy. 177Lu DOTA-TATE therapy is a form of peptide receptor radionuclide therapy (PRRT) which targets somatostatin receptors (SSR).[3][4] In that form of application it is a form of targeted drug delivery.

## Contents

* 1 Chemistry and mechanism of action
* 2 Clinical applications
* 2.1 Gallium-68 DOTA-TATE
* 2.2 Copper-64 DOTA-TATE
* 2.3 Lutetium-177 DOTA-TATE
* 3 See also
* 4 References

## Chemistry and mechanism of action

DOTA-TATE is a compound containing tyrosine3-octreotate,[2] an SSR agonist, and the bifunctional chelator DOTA (tetraxetan).[5][6] SSRs are found with high density in numerous malignancies, including CNS, breast, lung, and lymphatics.[7] The role of SSR agonists (i.e. somatostatin and its analogs such as octreotide, somatuline and vapreotide) in neuroendocrine tumours (NETs) is well established,[8] and massive SSR overexpression is present in several NETs. (Tyr3)-octreotate binds the transmembrane receptors of NETs with highest activity for SSR2 and is actively transported into the cell via endocytosis, allowing trapping of the radioactivity and increasing the probability of the desired double-strand DNA breakage (for tumour control). Trapping improves the probability of this kind of effect due to the relatively short range of the beta particles emitted by 177Lu, which have a maximum range in tissue of <2 mm.[9][8][10] Bystander effects include cellular damage by free radical formation.

## Clinical applications

### Gallium-68 DOTA-TATE

Further information: Gallium scan § Gallium DOTA scans

68Ga DOTA-TATE (gallium-68 dotatate, GaTate) is used to measure tumor SSR density and whole-body bio-distribution via PET imaging.[11][12] 68Ga DOTA-TATE imagery has a much higher sensitivity and resolution compared to 111In octreotide gamma camera or SPECT scans, due to intrinsic modality differences.[11] It is commonly used to confirm the presence of paragangliomas and pheochromocytomas.[13]

### Copper-64 DOTA-TATE

Copper (64Cu) oxodotreotide or copper Cu 64 dotatate, sold under the brand name Detectnet, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults. It was FDA approved in September 2020. These are the same indications for as the gallium DOTA-TATE scans, but Cu-64 has advantages over Ga-68 in having a 12-hour half life rather than the much shorter one-hour half life of Ga-68, making it easier to transport from central production locations. [14][15]

### Lutetium-177 DOTA-TATE

The combination of the beta emitter 177Lu with DOTA-TATE can be used in the treatment of cancers expressing the relevant somatostatin receptors.[16] The U.S. Food and Drug Administration (FDA) considers 177Lu-dotatate to be a first-in-class medication.[17]

Alternatives to 177Lu-DOTA-TATE include 90Y (T1/2 = 64.6 h) DOTA-TATE. The longer penetration range in the target tissues of the more energetic beta particles emitted by 90Y (high average beta energy of 0.9336 MeV) could make it more suitable for large tumors while 177Lu would be preferred for smaller volume tumors.[18][19]

## See also

* Lutetium
* 64Cu-dotatate

## References

1. ↑ "The Rate and Clinical Significance of Incidental Thyroid Uptake as Detected by Gallium-68 DOTATATE Positron Emission Tomography/Computed Tomography". Thyroid 26 (6): 831–5. June 2016. doi:10.1089/thy.2016.0174. PMID 27094616.
2. ↑ 2.0 2.1 Pubchem. "[Tyr3octreotate"]. https://pubchem.ncbi.nlm.nih.gov/compound/5326939.
3. ↑ Papotti, M.; Herder, W. W. de (2015). Neuroendocrine Tumors: A Multidisciplinary Approach. Karger Medical and Scientific Publishers. p. 77. ISBN 9783318027730. https://books.google.com/books?id=pHC9CgAAQBAJ&pg=PT87.
4. ↑ Aktolun, Cumali; Goldsmith, Stanley J. (2012). Nuclear Medicine Therapy: Principles and Clinical Applications. Springer. p. 364. ISBN 9781461440215. https://books.google.com/books?id=j-FgjR2qtfgC&pg=PA364.
5. ↑ Pubchem. "Tetraxetan". https://pubchem.ncbi.nlm.nih.gov/compound/121841.
6. ↑ "Somatostatin Receptor Antagonists for Imaging and Therapy". Journal of Nuclear Medicine 58 (Suppl 2): 61S–66S. September 2017. doi:10.2967/jnumed.116.186783. PMID 28864614.
7. ↑ "Multiple actions of somatostatin in neoplastic disease". Trends in Pharmacological Sciences 16 (3): 110–5. March 1995. doi:10.1016/S0165-6147(00)88992-0. PMID 7792931.
8. ↑ 8.0 8.1 "Somatostatin analogs in the treatment of neuroendocrine tumors: current and emerging aspects". Expert Opinion on Pharmacotherapy 18 (16): 1679–1689. November 2017. doi:10.1080/14656566.2017.1391217. PMID 29067877.
9. ↑ "177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy". Journal of Medical Radiation Sciences 64 (1): 52–60. March 2017. doi:10.1002/jmrs.227. PMID 28303694.
10. ↑ "Illuminating somatostatin analog action at neuroendocrine tumor receptors". Trends in Pharmacological Sciences 34 (12): 676–88. December 2013. doi:10.1016/j.tips.2013.10.001. PMID 24183675.
11. ↑ 11.0 11.1 "High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours". Journal of Medical Imaging and Radiation Oncology 56 (1): 40–7. February 2012. doi:10.1111/j.1754-9485.2011.02327.x. PMID 22339744.
12. ↑ "(68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives". Seminars in Nuclear Medicine 41 (4): 314–321. July 2011. doi:10.1053/j.semnuclmed.2011.02.001. PMID 21624565.
13. ↑ Chang, Chian A.; Pattison, David A.; Tothill, Richard W.; Kong, Grace; Akhurst, Tim J.; Hicks, Rodney J.; Hofman, Michael S. (2016-08-17). "68Ga-DOTATATE and 18F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity". Cancer Imaging 16 (1): 22. doi:10.1186/s40644-016-0084-2. ISSN 1740-5025. PMID 27535829.
14. ↑ "FDA approval letter". 3 September 2020. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213227Orig1s000ltr.pdf. This article incorporates text from this source, which is in the public domain.
15. ↑ "RadioMedix and Curium Announce FDA Approval of Detectnet (copper Cu 64 dotatate injection) in the U.S." (Press release). Curium. 8 September 2020. Retrieved 9 September 2020 - via GlobeNewswire.
16. ↑ "Somatostatin receptor-based molecular imaging and therapy for neuroendocrine tumors". BioMed Research International 2013: 102819. 2013. doi:10.1155/2013/102819. PMID 24106690.
17. ↑ (PDF) ﻿New Drug Therapy Approvals 2018﻿ (Report). January 2019. https://www.fda.gov/media/120357/download. Retrieved 16 September 2020.
18. ↑ "Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)". Gut 61 (1): 6–32. January 2012. doi:10.1136/gutjnl-2011-300831. PMID 22052063.
19. ↑ "The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours". European Journal of Nuclear Medicine and Molecular Imaging 40 (5): 800–16. May 2013. doi:10.1007/s00259-012-2330-6. PMID 23389427.

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/DOTA-TATE. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:DOTA-TATE&oldid=804404"
*[CID]: Compound ID