Gallium (68Ga) gozetotide
Clinical data
Trade namesIlluccix, Locametz
Other namesGallium 68 PSMA-11, Gallium Ga 68 gozetotide (USAN US)
AHFS/Drugs.comMicromedex Detailed Consumer Information
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category
Routes of
administration		Intravenous[2]
ATC code
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Legal status
Pharmacokinetic data
ExcretionUrine[2]
Identifiers
  • 2-[[5-[3-[[6-[[(5S)-5-carboxy-5-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentyl]amino]-6-oxohexyl]amino]-3-oxopropyl]-2-oxidophenyl]methyl-[2-[[5-(2-carboxyethyl)-2-oxidophenyl]methyl-(carboxylatomethyl)amino]ethyl]amino]acetate;gallium-68(3+);hydron
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PubChem CID
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UNII
KEGG
Chemical and physical data
3D model (JSmol)
  • [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]
  • InChI=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
  • Key:AEBYHKKMCWUMKX-LNTZDJBBSA-K

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.[9]

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.[9] It is the first drug approved by the US Food and Drug Administration (FDA) as a PET imaging agent.[11]

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.[7][8][9]

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.[2]

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

Mechanism of action

Gallium (68Ga) gozetotide binds with prostate-specific membrane antigen (PSMA).[2] This binds to cells that express PSMA, including malignant prostate cancer cells.[2] The radioactive isotope of gallium, 68Ga is responsible for emitting β+ radiations and X-rays.[2] This helps in recording images by positron emission tomography (PET) and CT scan.[2]

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.[20] The applicant for this medicinal product is Novartis Europharm Limited.[20] Locametz was approved for medical use in the European Union in December 2022.[9][21]

Names

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

References

  1. ^ a b "AusPAR: Glu-urea-Lys(ahx)-hbed-CC". Therapeutic Goods Administration (TGA). 27 June 2022. Retrieved 17 July 2022.[permanent dead link]
  2. ^ a b c d e f g h "Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution". DailyMed. 21 November 2021. Archived from the original on 3 July 2022. Retrieved 27 May 2022.
  3. ^ "Illuccix Summary Basis of Decision". Health Canada. Archived from the original on 27 May 2023. Retrieved 10 March 2023.
  4. ^ "Summary Basis of Decision for Locametz". Health Canada. 21 June 2023. Archived from the original on 20 August 2023. Retrieved 20 August 2023.
  5. ^ "Details for: Locametz". Health Canada. 11 May 2023. Archived from the original on 20 August 2023. Retrieved 20 August 2023.
  6. ^ "Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution". DailyMed. 30 November 2021. Archived from the original on 3 July 2022. Retrieved 27 May 2022.
  7. ^ a b "Illuccix- kit for the preparation of gallium ga 68 gozetotide injection kit". DailyMed. 12 May 2022. Archived from the original on 3 July 2022. Retrieved 27 May 2022.
  8. ^ a b "Locametz- kit for the preparation of gallium ga 68 gozetotide injection, powder, lyophilized, for solution". DailyMed. 23 March 2022. Archived from the original on 3 July 2022. Retrieved 27 May 2022.
  9. ^ a b c d e "Locametz EPAR". European Medicines Agency (EMA). 12 October 2022. Archived from the original on 21 December 2022. Retrieved 21 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. ^ "gallium Ga 68 gozetotide". National Cancer Institute. 2 February 2011. Archived from the original on 18 November 2021. Retrieved 18 November 2021.
  11. ^ a b c "FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer" (Press release). U.S. Food and Drug Administration (FDA). 2 December 2020. Archived from the original on 4 November 2021. Retrieved 9 November 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ "Drug Approval Package: Illuccix". U.S. Food and Drug Administration (FDA). 3 August 2022. Archived from the original on 21 December 2022. Retrieved 21 December 2022.
  13. ^ "Drug Approval Package: Locametz". U.S. Food and Drug Administration (FDA). 2 June 2022. Archived from the original on 21 December 2022. Retrieved 21 December 2022.
  14. ^ Makarem A, Sarvestani MK, Klika KD, Kopka K (2019). "A Multifunctional HBED-Type Chelator with Dual Conjugation Capabilities for Radiopharmaceutical Development". Synlett. 30 (15): 1795–1798. doi:10.1055/s-0039-1690194. S2CID 202871507.
  15. ^ Cho SY, Gage KL, Mease RC, et al. (2012). "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. doi:10.2967/jnumed.112.105361. PMC 3558632. PMID 23132604.
  16. ^ Afshar-Oromieh A, Haberkorn U, Eder M, et al. (2013). "PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer". Eur J Nucl Med Mol Imaging. 40 (10): 1629–1630. doi:10.1007/s00259-013-2489-5. PMID 23817686. S2CID 26385694.
  17. ^ "Gallium (68Ga) Chloride Solution for Radiolabelling". European Pharmacopoeia (9th ed.). Stuttgart. 2018. p. 1148. ISBN 978-3-7692-6816-4.((cite book)): CS1 maint: location missing publisher (link)
  18. ^ "Gallium (68Ga) DOTATOC injection". European Pharmacopoeia (10th ed.). Stuttgart. 2019. p. 1208. ISBN 978-3-7692-7453-0.((cite book)): CS1 maint: location missing publisher (link)
  19. ^ Carlucci G, Ippisch R, Slavik R, Mishoe A, Blecha J, Zhu S (February 2021). "68Ga-PSMA-11 NDA Approval: A Novel and Successful Academic Partnership". Journal of Nuclear Medicine. 62 (2): 149–155. doi:10.2967/jnumed.120.260455. PMC 8679592. PMID 33443068.
  20. ^ a b "Locametz: Pending EC decision". European Medicines Agency. 13 October 2022. Archived from the original on 14 October 2022. Retrieved 14 October 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  21. ^ "Locametz Product information". Union Register of medicinal products. Archived from the original on 16 December 2022. Retrieved 3 March 2023.
  22. ^ World Health Organization (2021). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85" (PDF). WHO Drug Information. 35 (1). Archived (PDF) from the original on 19 April 2021. Retrieved 28 May 2022.

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