Gallium (68Ga) gozetotide

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
Routes of administration	Intravenous
ATC code	V09IX14 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only / Schedule C US: ℞-only EU: Rx-only
Pharmacokinetic data
Excretion	Urine
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). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.

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, 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.

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.

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.

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, in 2019 European Pharmacopoeia mentions gallium (⁶⁸Ga) DOTATOC injection for radiolabelling and PET imaging.

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. In December 2020, the drug was first approved by 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. Locametz was approved for medical use in the European Union in December 2022.

Names

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

External links

• "Gallium Ga 68 gozetotide". Drug Information Portal. U.S. National Library of Medicine.