Gallium (68Ga) gozetotide

Radiopharmaceutical medication From Wikipedia, the free encyclopedia

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11, sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to a inhibitor of the enzyme prostate-specific membrane antigen (PSMA) known as Glu-Urea-Lys(Ahx)-HBED-CC. It is used for imaging prostate cancer by positron emission tomography (PET).[12] The PSMA inhibitor specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.[13]

Trade namesIlluccix, Locametz
Other namesGallium 68 PSMA-11, Gallium Ga 68 gozetotide (USAN US)
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Gallium (68Ga) gozetotide
Clinical data
Trade namesIlluccix, Locametz
Other namesGallium 68 PSMA-11, Gallium Ga 68 gozetotide (USAN US)
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administration		Intravenous[2]
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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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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
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The most common side effects with gallium (68Ga)-radiolabelled gozetotide are tiredness, nausea (feeling sick), constipation and vomiting.[11]

Gallium (68Ga) gozetotide was approved for medical use in the United States in December 2021,[14][15] and in the European Union in December 2022.[11] It is the first drug approved by the US Food and Drug Administration (FDA) as a PET imaging agent of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer.[13]

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.[16]

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.[8][9][11]

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.[17]

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.[18]

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,[19] in 2019 European Pharmacopoeia mentions gallium (68Ga) DOTATOC injection for radiolabelling and PET imaging.[20]

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.[21] In December 2020, the drug was first approved by the US Food and Drug Administration (FDA) for PET imaging.[13]

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

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.[22] The applicant for this medicinal product is Novartis Europharm Limited.[22] Locametz was approved for medical use in the European Union in December 2022.[11][23]

Names

Gallium (68Ga) gozetotide is the international nonproprietary name (INN).[24]

References

External links

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