DOTA-TATE













































DOTA-TATE

DOTATATE.svg
Names
Other names
DOTA-(Tyr3)-octreotate

Identifiers

CAS Number
  • 177943-89-4

3D model (JSmol)
  • Interactive image

ChemSpider
  • 9345959


PubChem CID
  • 11170867




Properties

Chemical formula
C65H90N14O19S2

Molar mass
 1,435.63 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 (Also known as DOTA-octreotate, oxodotreotide and DOTA-(Tyr3)-octreotate[1]/ DOTA-0-Tyr3-Octreotate) is an amino acid peptide, with a covalently bonded DOTA bifunctional chelator.


DOTA-TATE can be bound with radionuclides such as gallium-68 and lutetium-177 to form radiopharmaceuticals for PET imaging or radionuclide therapy. 177Lu DOTA-TATE therapy is a form of peptide receptor radionuclide therapy (PRRT) which targets somatostatin receptors (SSR). [2][3] In that form of application it is a form of targeted drug delivery.




Contents






  • 1 Chemistry and mechanism of action


  • 2 Usage examples


    • 2.1 Availability




  • 3 References





Chemistry and mechanism of action


DOTA-TATE is a compound containing tyrosine3-octreotate[1], an SSR antagonist, and the bifunctional chelator (BFC) DOTA (tetraxentan).[4][5]SSRs are found with high density in numerous malignancies, including CNS, breast, lung, and lymphatics.[6] The role of SSR antagonists (i.e. somatostatin and its analogs such as octreotide, somatuline and vapreotide) in neuroendocrine tumours (NETs) is well established,[7] 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.[8][7][9]Bystander effects include cellular damage by free radical formation.



Usage examples


See also: Gallium scan § Gallium DOTA scans, and peptide receptor radionuclide therapy

68Ga DOTA-TATE (GaTate) is used to measure tumor SSR density and wholebody bio-distribution via PET imaging.[10][11]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.[10]


177Lu DOTA-TATE, trade name Lutathera, was approved by the FDA for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults, in January 2018.[12] The recommended dosage is 4 cycles of 7.5 GBq every 8 weeks. About four to six hours after infusion, the exposure rate of the patient has fallen to less than 25 μSv/hour at one metre and the patients can be discharged from hospital.[13]


Alternatives to 177Lu-DOTATE include yttrium-90 DOTATATE or DOTATOC. The larger range of 90Y may make it more suitable for large tumors with 177Lu reserved for smaller volumes[14][15]



Availability


The European Commission approved marketing of Lutathera "for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults" in October 2017.[16]



References





  1. ^ ab Pubchem. "[Tyr3]octreotate". pubchem.ncbi.nlm.nih.gov. Retrieved 2018-04-02..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}


  2. ^ Papotti, M.; Herder, W. W. de (2015). Neuroendocrine Tumors: A Multidisciplinary Approach. Karger Medical and Scientific Publishers. p. 77. ISBN 9783318027730.


  3. ^ Aktolun, Cumali; Goldsmith, Stanley J. (2012). Nuclear Medicine Therapy: Principles and Clinical Applications. Springer. p. 364. ISBN 9781461440215.


  4. ^ Pubchem. "Tetraxetan". pubchem.ncbi.nlm.nih.gov. Retrieved 2018-04-02.


  5. ^ Fani, Melpomeni; Nicolas, Guillaume P.; Wild, Damian (1 September 2017). "Somatostatin Receptor Antagonists for Imaging and Therapy". Journal of Nuclear Medicine. 58 (Supplement 2): 61S–66S. doi:10.2967/jnumed.116.186783. PMID 28864614.


  6. ^ Reubi JC, Laissue JA (March 1995). "Multiple actions of somatostatin in neoplastic disease". Trends in Pharmacological Sciences. 16 (3): 110–5. PMID 7792931.


  7. ^ ab Mazziotti G, Mosca A, Frara S, Vitale G, Giustina A (November 2017). "Somatostatin analogs in the treatment of neuroendocrine tumors: current and emerging aspects". Expert Opinion on Pharmacotherapy. 18 (16): 1679–1689. doi:10.1080/14656566.2017.1391217. PMID 29067877.


  8. ^ Emmett, Louise; Willowson, Kathy; Violet, John; Shin, Jane; Blanksby, Ashley; Lee, Jonathan (March 2017). "Lutetium177 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. doi:10.1002/jmrs.227. PMC 5355374.


  9. ^ Reubi JC, Schonbrunn A (December 2013). "Illuminating somatostatin analog action at neuroendocrine tumor receptors". Trends in Pharmacological Sciences. 34 (12): 676–88. doi:10.1016/j.tips.2013.10.001. PMC 3883302. PMID 24183675.


  10. ^ ab Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ (February 2012). "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. doi:10.1111/j.1754-9485.2011.02327.x. PMID 22339744.


  11. ^ Breeman WA, de Blois E, Sze Chan H, Konijnenberg M, Kwekkeboom DJ, Krenning EP (July 2011). "(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): 314–21. doi:10.1053/j.semnuclmed.2011.02.001. PMID 21624565.


  12. ^ "Radiolabeled Peptide Offers PFS Benefit in Midgut NET". MedPage Today. 11 January 2017. Retrieved 25 April 2018.


  13. ^ Calais, Phillipe J.; Turner, J. Harvey (1 April 2014). "Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors". Annals of Nuclear Medicine. 28 (6): 531–539. doi:10.1007/s12149-014-0843-8. PMID 24687907.


  14. ^ Ramage, John K; Ahmed, A; Ardill, J; Bax, N; Breen, D J; Caplin, M E; Corrie, P; Davar, J; Davies, A H; Lewington, V; Meyer, T; Newell-Price, J; Poston, G; Reed, N; Rockall, A; Steward, W; Thakker, R V; Toubanakis, C; Valle, J; Verbeke, C; Grossman, A B (January 2012). "Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)". Gut. 61 (1): 6–32. doi:10.1136/gutjnl-2011-300831. PMC 3280861.


  15. ^ Bodei, L; Mueller-Brand, J; Baum, RP; Pavel, ME; Hörsch, D; O'Dorisio, MS; O'Dorisio, TM; Howe, JR; Cremonesi, M; Kwekkeboom, DJ; Zaknun, JJ (May 2013). "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. doi:10.1007/s00259-012-2330-6. PMC 3622744.


  16. ^ "European approval of lutetium oxodotreotide for gastroenteropancreatic neuroendocrine (GEP-NET) tumours". ecancer.org. 2017-10-03. Retrieved 2018-04-02.









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