Gallium (68Ga) gozetotide

Short description: Radiopharmaceutical medication

Gallium (68Ga) gozetotide

Clinical data
Trade names| Illuccix, Locametz
Other names| Gallium 68 PSMA-11, Gallium Ga 68 gozetotide (USAN US)
AHFS/Drugs.com| Micromedex Detailed Consumer Information
License data|

* US DailyMed: Gozetotide

Pregnancy
category|

* AU: Exempt[1]

Routes of
administration| Intravenous[2]
ATC code|

* V09IX14 (WHO)

Legal status
Legal status|

* AU: S4 (Prescription only) [1]
* CA: ℞-only / Schedule C[3][4][5]
* US: ℞-only [2][6][7][8]
* EU: Rx-only [9]

Pharmacokinetic data
Excretion| Urine[2]
Identifiers

IUPAC name

* 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

CAS Number|

* 1906894-20-9

PubChem CID|

* 154572876

DrugBank|

* DB16019
* DB16303

ChemSpider|

* 52083842

UNII|

* ZJ0EKR6M10

KEGG|

* D12257

Chemical and physical data
3D model (JSmol)|

* Interactive image

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]

InChI

* 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]

## Contents

* 1 Structure
* 2 Medical uses
* 3 History
* 4 Mechanism of action
* 5 Society and culture
* 5.1 Legal status
* 5.2 Names
* 6 References
* 7 External links

## 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. ↑ 1.0 1.1 "AusPAR: Glu-urea-Lys(ahx)-hbed-CC". 27 June 2022. https://www.tga.gov.au/auspar/auspar-glu-urea-lysahx-hbed-cc. [yes|permanent dead link|dead link}}]
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution". 21 November 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7744bafb-755e-29a2-e053-2991aa0a86a9.
3. ↑ "Illuccix Summary Basis of Decision". https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00624&lang=en.
4. ↑ "Summary Basis of Decision for Locametz". 21 June 2023. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1687370834165.
5. ↑ "Details for: Locametz". 11 May 2023. https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102582.
6. ↑ "Gallium GA-68 PSMA-11- gallium ga-68 gozetotide injection, solution". 30 November 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6253a7b-0f73-36be-e053-2a95a90a9015.
7. ↑ 7.0 7.1 "Illuccix- kit for the preparation of gallium ga 68 gozetotide injection kit". 12 May 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d4643b31-9b4f-673f-e053-2a95a90a559d.
8. ↑ 8.0 8.1 "Locametz- kit for the preparation of gallium ga 68 gozetotide injection, powder, lyophilized, for solution". 23 March 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1ea62b65-8138-4a88-8a33-4060ececa42f.
9. ↑ 9.0 9.1 9.2 9.3 9.4 "Locametz EPAR". 12 October 2022. https://www.ema.europa.eu/en/medicines/human/EPAR/locametz. 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". 2 February 2011. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/gallium-ga-68-gozetotide?redirect=true.
11. ↑ 11.0 11.1 11.2 "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. 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. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/214032Orig1s000TOC.cfm.
13. ↑ "Drug Approval Package: Locametz". U.S. Food and Drug Administration (FDA). 2 June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215841Orig1s000TOC.cfm.
14. ↑ "A Multifunctional HBED-Type Chelator with Dual Conjugation Capabilities for Radiopharmaceutical Development". Synlett 30 (15): 1795–1798. 2019. doi:10.1055/s-0039-1690194.
15. ↑ "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. doi:10.2967/jnumed.112.105361. PMID 23132604.
16. ↑ "PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer". Eur J Nucl Med Mol Imaging 40 (10): 1629–1630. 2013. doi:10.1007/s00259-013-2489-5. PMID 23817686.
17. ↑ "Gallium (68Ga) Chloride Solution for Radiolabelling". European Pharmacopoeia (9th ed.). Stuttgart. 2018. p. 1148. ISBN 978-3-7692-6816-4.
18. ↑ "Gallium (68Ga) DOTATOC injection". European Pharmacopoeia (10th ed.). Stuttgart. 2019. p. 1208. ISBN 978-3-7692-7453-0.
19. ↑ "68Ga-PSMA-11 NDA Approval: A Novel and Successful Academic Partnership". Journal of Nuclear Medicine 62 (2): 149–155. February 2021. doi:10.2967/jnumed.120.260455. PMID 33443068.
20. ↑ 20.0 20.1 "Locametz: Pending EC decision". 13 October 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/locametz. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
21. ↑ "Locametz Product information". https://ec.europa.eu/health/documents/community-register/html/h1692.htm.
22. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85". WHO Drug Information 35 (1). 2021. https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/rl85.pdf. Retrieved 28 May 2022.

## External links

* "Gallium Ga 68 gozetotide". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/gallium ga 68 gozetotide.

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Diagnostic radiopharmaceuticals (ATC: V09)

Central nervous system|

* 99mTc (Exametazime)
* 123I (Ioflupane
* Iofetamine
* Iomazenil)
* 18F (Florbetapir, Flutemetamol)

Skeletal system|

* 99mTc (Medronic acid)

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* 123I (Sodium iodohippurate)
* 64Cu (Cu-ETS2)

Gastrointestinal/Hepatic|

* 75Se (SeHCAT)

Respiratory system|

* 133Xe
* 81mKr
* 99mTc (99mTc-MAA)

Cardiovascular system|

* 99mTc (Sestamibi
* Tetrofosmin)
* 111In (Imciromab)
* 82Rb (Rubidium chloride)

Inflammation/infection|

* 99mTc (Exametazime
* Sulesomab
* Tilmanocept)
* 111In
* 67Ga

Tumor|

* 99mTc (Arcitumomab
* Votumumab
* Hynic-octreotide)
* 111In (Capromab pendetide
* Satumomab pendetide)
* 125I (Minretumomab)
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* Fludeoxyglucose
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Adrenal cortex|

* 123I
* 125I / 131I (Iodocholesterol)

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(including tracers)|

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* 13N (Ammonia)
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* MPPF
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* 64Cu
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* 82Rb (Rubidium chloride)

|

gamma ray/photon (SPECT/scintigraphy)|

* 51Cr
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* 75Se
* 81mKr
* 99mTc
* 111In
* 123I
* 125I
* 131I
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* 153Sm
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