Gallium (68Ga) gozetotide explained

Drug Name:Gallium (68Ga) gozetotide
Usan:Gallium Ga 68 gozetotide
Tradename:Illuccix, Locametz
Dailymedid:Gozetotide
Pregnancy Au Comment:Exempt
Routes Of Administration:Intravenous
Atc Prefix:V09
Atc Suffix:IX14
Legal Au:S4
Legal Au Comment:[1]
Legal Ca:Rx-only
Legal Ca Comment:/Schedule C[2] [3] [4]
Legal Us:Rx-only
Legal Us Comment:[5] [6] [7] [8]
Legal Eu:Rx-only
Legal Eu Comment:[9]
Excretion:Urine
Cas Number:1906894-20-9
Pubchem:154572876
Drugbank:DB16019
Drugbank2:DB16303
Chemspiderid:52083842
Unii:ZJ0EKR6M10
Kegg:D12257
Synonyms:Gallium 68 PSMA-11
Iupac Name:2-[<nowiki/>[5-[3-[<nowiki/>[6-[<nowiki/>[(5S)-5-carboxy-5-[<nowiki/>[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentyl]amino]-6-oxohexyl]amino]-3-oxopropyl]-2-oxidophenyl]methyl-[2-[<nowiki/>[5-(2-carboxyethyl)-2-oxidophenyl]methyl-(carboxylatomethyl)amino]ethyl]amino]acetate;gallium-68(3+);hydron
Stdinchi:1S/C44H62N6O17.Ga/c51-34-13-8-28(22-30(34)24-49(26-40(59)60)20-21-50(27-41(61)62)25-31-23-29(9-14-35(31)52)11-16-38(55)56)10-15-37(54)46-18-4-1-2-7-36(53)45-19-5-3-6-32(42(63)64)47-44(67)48-33(43(65)66)12-17-39(57)58;/h8-9,13-14,22-23,32-33,51-52H,1-7,10-12,15-21,24-27H2,(H,45,53)(H,46,54)(H,55,56)(H,57,58)(H,59,60)(H,61,62)(H,63,64)(H,65,66)(H2,47,48,67);/q;+3/p-3/t32-,33-;/m0./s1/i;1-2
Stdinchikey:AEBYHKKMCWUMKX-LNTZDJBBSA-K
Smiles:[H+].C1=CC(=C(C=C1CCC(=O)NCCCCCC(=O)NCCCC[C@@H](C(=O)O)NC(=O)N[C@@H](CCC(=O)O)C(=O)O)CN(CCN(CC2=C(C=CC(=C2)CCC(=O)O)[O-])CC(=O)[O-])CC(=O)[O-])[O-].[68Ga+3]

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET).[10] The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.[11]

The most common side effects with gallium (68Ga)-radiolabelled gozetotide are tiredness, nausea (feeling sick), constipation and vomiting.

Gallium (68Ga) gozetotide was approved for medical use in the United States in December 2021,[12] [13] and in the European Union in December 2022. It is the first drug approved by the US Food and Drug Administration (FDA) as a PET imaging agent.

Structure

Radiopharmaceuticals based on HBED are composed of three components: a chelator that has a HBED structure and two functions, a radiometal coordinated with the chelator, and a binding motif or pharmacophore that is conjugated to the chelator (such as a peptide or antibody). One of the most popular HBED chelators is HBED-CC. This chelator can create stable complexes with trivalent gallium at normal temperatures and it attaches to bioactive molecules through its propionic acid moieties.[14]

Medical uses

Gallium (68Ga) gozetotide is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer.

Ga 68 PSMA-11 injections are used for PET imaging of prostate-specific membrane antigen (PSMA) positive lesions in males with prostate cancer. It can be given for the patients with suspected metastasis, and the candidates with initial definitive therapy.

History

In the early 2000s, researchers began exploring the use of PSMA as a target for imaging and therapy. The first PSMA-targeted radiotracer was developed using a different radioactive element, technetium-99m. This radiotracer, called 99mTc-MIP-1404, showed promise in preclinical studies but did not perform well in clinical trials.[15]

In 2011, researchers started investigating the use of gallium-68, a different radioactive element, as a more suitable alternative for PSMA-targeted radiotracers. In 2013, the first Ga-PSMA radiotracer was developed by researchers at DKFZ in Germany, and it showed promising results in early clinical studies.[16]

Since then, Ga-PSMA has been extensively studied in clinical trials, and it has been found to be a highly effective imaging agent for detecting prostate cancer lesions. It is now widely used in clinical practice, particularly for patients with recurrent prostate cancer and those with high-risk disease.

Initially gallium (68Ga) chloride solution injections used for radiolabelling,[17] in 2019 European Pharmacopoeia mentions gallium (68Ga) DOTATOC injection for radiolabelling and PET imaging.[18]

Ga 68 PSMA-11 was co-developed by researchers at University of California, Los Angeles and University of California, San Francisco, who conducted a phase III clinical trial.[19] In December 2020, the drug was first approved by the US Food and Drug Administration (FDA) for PET imaging.

Mechanism of action

Gallium (68Ga) gozetotide binds with prostate-specific membrane antigen (PSMA). This binds to cells that express PSMA, including malignant prostate cancer cells. The radioactive isotope of gallium, 68Ga is responsible for emitting β+ radiations and X-rays. This helps in recording images by positron emission tomography (PET) and CT scan.

Society and culture

Legal status

On 13 October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Locametz, intended for the diagnosis of prostate cancer. The applicant for this medicinal product is Novartis Europharm Limited.[20] Locametz was approved for medical use in the European Union in December 2022.[21]

Names

Gallium (68Ga) gozetotide is the international nonproprietary name (INN).[22]

External links

Notes and References

  1. Web site: AusPAR: Glu-urea-Lys(ahx)-hbed-CC . Therapeutic Goods Administration (TGA) . 27 June 2022 . 17 July 2022 .
  2. Web site: Illuccix Summary Basis of Decision . Health Canada . 10 March 2023 . 27 May 2023 . https://web.archive.org/web/20230527233827/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00624&lang=en . live .
  3. Web site: Summary Basis of Decision for Locametz . . 21 June 2023 . 20 August 2023 . 20 August 2023 . https://web.archive.org/web/20230820200527/https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1687370834165 . live .
  4. Web site: Details for: Locametz . . 11 May 2023 . 20 August 2023 . 20 August 2023 . https://web.archive.org/web/20230820200542/https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102582 . live .
  5. Web site: Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution . DailyMed . 21 November 2021 . 27 May 2022 . 3 July 2022 . https://web.archive.org/web/20220703060124/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7744bafb-755e-29a2-e053-2991aa0a86a9 . live .
  6. Web site: Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution . DailyMed . 30 November 2021 . 27 May 2022 . 3 July 2022 . https://web.archive.org/web/20220703060125/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6253a7b-0f73-36be-e053-2a95a90a9015 . live .
  7. Web site: Illuccix- kit for the preparation of gallium ga 68 gozetotide injection kit . DailyMed . 12 May 2022 . 27 May 2022 . 3 July 2022 . https://web.archive.org/web/20220703060125/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d4643b31-9b4f-673f-e053-2a95a90a559d . live .
  8. Web site: Locametz- kit for the preparation of gallium ga 68 gozetotide injection, powder, lyophilized, for solution . DailyMed . 23 March 2022 . 27 May 2022 . 3 July 2022 . https://web.archive.org/web/20220703060125/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1ea62b65-8138-4a88-8a33-4060ececa42f . live .
  9. Web site: Locametz EPAR . European Medicines Agency (EMA) . 12 October 2022 . 21 December 2022 . 21 December 2022 . https://web.archive.org/web/20221221184835/https://www.ema.europa.eu/en/medicines/human/EPAR/locametz . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. Web site: gallium Ga 68 gozetotide . National Cancer Institute . 2 February 2011 . 18 November 2021 . 18 November 2021 . https://web.archive.org/web/20211118223500/https://www.cancer.gov/publications/dictionaries/cancer-drug/def/gallium-ga-68-gozetotide?redirect=true . live .
  11. FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer . U.S. Food and Drug Administration (FDA) . 9 November 2021 . 2 December 2020 . 4 November 2021 . https://web.archive.org/web/20211104143636/https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer . live .
  12. Web site: Drug Approval Package: Illuccix . U.S. Food and Drug Administration (FDA) . 3 August 2022 . 21 December 2022 . 21 December 2022 . https://web.archive.org/web/20221221222338/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/214032Orig1s000TOC.cfm . live .
  13. Web site: Drug Approval Package: Locametz . U.S. Food and Drug Administration (FDA) . 2 June 2022 . 21 December 2022 . 21 December 2022 . https://web.archive.org/web/20221221222335/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215841Orig1s000TOC.cfm . live .
  14. Makarem A, Sarvestani MK, Klika KD, Kopka K . A Multifunctional HBED-Type Chelator with Dual Conjugation Capabilities for Radiopharmaceutical Development . Synlett . 30 . 15 . 1795–1798 . 2019 . 10.1055/s-0039-1690194 . 202871507 .
  15. Cho SY, Gage KL, Mease RC, et al.. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer . J Nucl Med . 53 . 12 . 1883–1891 . 2012 . 23132604 . 10.2967/jnumed.112.105361 . 3558632 .
  16. Afshar-Oromieh A, Haberkorn U, Eder M, et al. . PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer . Eur J Nucl Med Mol Imaging . 40 . 10 . 1629–1630 . 2013 . 23817686 . 10.1007/s00259-013-2489-5 . 26385694 .
  17. Book: Gallium (68Ga) Chloride Solution for Radiolabelling . European Pharmacopoeia . 9th . 2018 . Stuttgart . 978-3-7692-6816-4 . 1148 .
  18. Book: Gallium (68Ga) DOTATOC injection . European Pharmacopoeia . 2019 . Stuttgart . 978-3-7692-7453-0 . 10th . 1208.
  19. Carlucci G, Ippisch R, Slavik R, Mishoe A, Blecha J, Zhu S . 68Ga-PSMA-11 NDA Approval: A Novel and Successful Academic Partnership . Journal of Nuclear Medicine . 62 . 2 . 149–155 . February 2021 . 33443068 . 8679592 . 10.2967/jnumed.120.260455 .
  20. Web site: Locametz: Pending EC decision . European Medicines Agency . 13 October 2022 . 14 October 2022 . 14 October 2022 . https://web.archive.org/web/20221014134625/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/locametz . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. Web site: Locametz Product information . Union Register of medicinal products . 3 March 2023 . 16 December 2022 . https://web.archive.org/web/20221216114512/https://ec.europa.eu/health/documents/community-register/html/h1692.htm . live .
  22. ((World Health Organization)) . 2021 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85 . WHO Drug Information . 35 . 1 . World Health Organization . 28 May 2022 . 19 April 2021 . https://web.archive.org/web/20210419172602/https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-%28inn%29/rl85.pdf . live .

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