Ga 68 PSMA-11

Identification

Summary

Ga 68 PSMA-11 is a radiopharmaceutical agent used in the diagnosis of prostate-specific membrane antigen (PSMA) positive lesions in male patients during positron emission tomography.

Generic Name
Gallium Ga-68 gozetotide
Commonly known or available as Ga 68 PSMA-11
DrugBank Accession Number
DB16019
Background

Gallium (Ga) 68 prostate-specific membrane antigen (PSMA)-11, or Ga-68 gozetotide, is a radiopharmaceutical agent used to identify and assess prostate-specific membrane antigen (PSMA)-positive lesions in adult men with prostate cancer during positron emission tomography (PET).7 Prostate cancer is one of the most commonly diagnosed cancers among men in Western countries and many patients treated with androgen-deprivation therapy relapse with castration-resistant prostate cancer.1 In nearly all prostate cancers, malignant cells express a transmembrane protein called prostate-specific membrane antigen (PSMA).1 Ga-68 PSMA-11 is an imaging agent that binds PSMA during positron emission tomography: it emits positrons to indicate the presence of PSMA-positive prostate cancer lesions in patients with suspected prostate cancer or in patients who may have recurrent prostate cancer.8 On December 1, 2020, Ga-68 PSMA-11 was approved by the FDA as the first molecular-targeted drug for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer.8 It is administered intravenously.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1011.909
Monoisotopic: 1011.321652961
Chemical Formula
C44H59GaN6O17
Synonyms
  • (68)Ga Labeled Glu-NH-CO-NH-Lys(ahx)-hbed-CC
  • (68Ga)Hbed-psma
  • (68Ga)Psma-hbed-CC
  • 68Ga-Psma-11
  • 68Ga-Psma-hbed-CC
  • DKFZ-PSMA-11 Ga-68
  • Ga-68 PSMA-11
  • Ga-68-Labeled PSMA-11
  • Ga-Psma-hbed-CC Ga-68
  • Gallium (68Ga) gozetotide
  • Gallium Ga 68 PSMA-11
  • Gallium Ga 68-labeled psma ligand Glu-urea-Lys(ahx)-hbed-CC
  • PSMA-11 Ga 68
  • PSMA-11 Ga-68
  • Psma-hbed-CC Ga-68

Pharmacology

Indication

Gallium Ga-68 gozetotide, or Gallium Ga-68 PSMA-11, is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA)-positive lesions in patients with suspected prostate cancer metastasis who are also candidates for initial surgical or radiation therapy. It is also indicated for patients with suspected prostate cancer recurrence based on elevated serum prostate-specific antigen (PSA) levels.7

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Ga-68 PSMA-11 works by binding to prostate-specific membrane antigen (PSMA) expressed on malignant prostate cancer cells. Gallium-68 (Ga-68) is a β+-emitting radionuclide and Ga-68 PSMA-11 can be imaged by PET to indicate the presence of PSMA-positive prostate cancer lesions in the tissues of the body.7 Ga-68 PMSA-11 has a high affinity to PSMA and was shown to be effective in imaging of both local prostate cancer tumours and distant metastatic lesions in clinical trials.3,4 In a clinical trial comprising patients with relapsed prostate cancer, Ga-68 PSMA-11 PET detection rate was different depending on the clinical stage of biochemical recurrence.6

Mechanism of action

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein expressed throughout the body, such as in lacrimal and salivary glands, the kidneys, small intestine, liver and spleen.3,5,2 It is highly associated with tumour-associated angiogenesis and has been described in various tumours, such as prostate cancer, glioblastoma, thyroid cancer, gastric cancer, breast cancer, renal cancer, and colorectal cancers.6 The expression of PSMA has been linked to the degree of tumour differentiation, as it is overexpressed particularly in poorly differentiated and metastatic lesions.1,5 PSMA has been extensively studied as a reliable target for imaging and therapy for prostate cancer, as it is overexpressed one-hundred to one thousand-fold in over 90 % of primary prostate cancers.6

Positron emission tomography (PET) is a type of molecular imaging used to improve the accuracy of detecting prostate cancer at an earlier time and examine tumour characteristics. Ga-68 PSMA-11 is a PSMA-targeted imaging agent for PET that binds to PSMA via clathrin-coated pits, resulting in endosome accumulation and the internalization of the PSMA-drug complex.6

TargetActionsOrganism
AProstate-specific antigen
binder
Humans
Absorption

Following intravenous injection, Ga-68 PSMA-11 uptake occurs in the adrenal and prostate glands, with high uptake in PSMA-expressing tissues.6 Uptake of the drug is very minimal in the cerebral cortex, heart, and lungs.7 Mean maximum standardized uptake value (SUVmax) at later acquisition times is about 15.3.4

Volume of distribution

Ga-68 PSMA-11 accumulates in the liver (15%), kidneys (7%), spleen (2%), and salivary glands (0.5%).7 Ga-68 PSMA-11 accumulation increases at later acquisition times.4

Protein binding

There is no information on plasma protein binding.

Metabolism

Ga-68 PSMA-11 decays to stable zinc-68.7

Route of elimination

About 14% of the total injected dose is excreted in the urine within two hours following intravenous administration.7

Half-life

Gallium-68 (Ga-68) decays with a half-life of 68 minutes.7

Clearance

There is limited information on the clearance rate, but Ga-68 PSMA-11 shows fast blood clearance.6

Adverse Effects
Adverseeffects
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Toxicity

There is limited information on the LD50 value of Ga-68 PSMA-11. In the event of an overdose, it is recommended to enhance drug elimination by hydration, frequent bladder voiding, or the use of diuretics.7

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
ApalutamideApalutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
BicalutamideBicalutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
Cyproterone acetateCyproterone acetate may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
DarolutamideDarolutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
EnzalutamideEnzalutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
FlutamideFlutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
NilutamideNilutamide may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
RelugolixRelugolix may increase effectiveness of Gallium Ga-68 gozetotide as a diagnostic agent.
Interactions
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Food Interactions
No interactions found.

Products

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International/Other Brands
Prostamedix

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
ZJ0EKR6M10
CAS number
1906894-20-9
InChI Key
AEBYHKKMCWUMKX-LNTZDJBBSA-K
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
IUPAC Name
(68Ga)gallium(3+) hydrogen 2-[(2-{[(5-{2-[(5-{[(5S)-5-carboxy-5-({[(1S)-1,3-dicarboxypropyl]carbamoyl}amino)pentyl]carbamoyl}pentyl)carbamoyl]ethyl}-2-oxidophenyl)methyl](carboxylatomethyl)amino}ethyl)({[5-(2-carboxyethyl)-2-oxidophenyl]methyl})amino]acetate
SMILES
[H+].[68Ga+3].OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)CCCCCNC(=O)CCC1=CC=C([O-])C(CN(CCN(CC([O-])=O)CC2=CC(CCC(O)=O)=CC=C2[O-])CC([O-])=O)=C1)C(O)=O)C(O)=O

References

General References
  1. Hope TA, Truillet C, Ehman EC, Afshar-Oromieh A, Aggarwal R, Ryan CJ, Carroll PR, Small EJ, Evans MJ: 68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience. J Nucl Med. 2017 Jan;58(1):81-84. doi: 10.2967/jnumed.116.181800. Epub 2016 Sep 22. [Article]
  2. Lenzo NP, Meyrick D, Turner JH: Review of Gallium-68 PSMA PET/CT Imaging in the Management of Prostate Cancer. Diagnostics (Basel). 2018 Feb 11;8(1). pii: diagnostics8010016. doi: 10.3390/diagnostics8010016. [Article]
  3. Bakht MK, Oh SW, Youn H, Cheon GJ, Kwak C, Kang KW: Influence of Androgen Deprivation Therapy on the Uptake of PSMA-Targeted Agents: Emerging Opportunities and Challenges. Nucl Med Mol Imaging. 2017 Sep;51(3):202-211. doi: 10.1007/s13139-016-0439-4. Epub 2016 Aug 6. [Article]
  4. Park SY, Zacharias C, Harrison C, Fan RE, Kunder C, Hatami N, Giesel F, Ghanouni P, Daniel B, Loening AM, Sonn GA, Iagaru A: Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology. 2018 Aug;288(2):495-505. doi: 10.1148/radiol.2018172232. Epub 2018 May 22. [Article]
  5. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C: Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997 Jan;3(1):81-5. [Article]
  6. Ceci F, Castellucci P, Graziani T, Farolfi A, Fonti C, Lodi F, Fanti S: (68)Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy. Eur J Nucl Med Mol Imaging. 2019 Jan;46(1):31-39. doi: 10.1007/s00259-018-4189-7. Epub 2018 Oct 22. [Article]
  7. FDA Approved Drug Products: Gallium Ga 68 PSMA-11 Injection, for intravenous use [Link]
  8. FDA Press Announcements: FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer [Link]
ChemSpider
52083842

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Enrolling by InvitationDiagnosticProstate Cancer1
3Unknown StatusDiagnosticProstate Cancer1
2Active Not RecruitingDiagnosticAdenocarcinoma, Prostate / Biochemically Recurrent Prostate Carcinoma / Prostate Cancer / PSA Level Greater Than Fifty / PSA Progression / Refractory, metastatic hormone-refractory Prostate cancer / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
2CompletedDiagnosticLatent Cancer (Prostate)1
2CompletedDiagnosticProstate Cancer1
2CompletedDiagnosticRecurrent Prostate Carcinoma1
2Not Yet RecruitingDiagnosticCastration-Resistant Prostate Carcinoma / Refractory, metastatic hormone-refractory Prostate cancer / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
2Not Yet RecruitingDiagnosticRecurrent Prostate Carcinoma / Refractory, metastatic hormone-refractory Prostate cancer / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
2RecruitingDiagnosticAdenocarcinoma, Prostate / Biochemically Recurrent Prostate Carcinoma / Castration-Resistant Prostate Carcinoma / Refractory, metastatic hormone-refractory Prostate cancer / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
2RecruitingDiagnosticAdenocarcinoma, Prostate / Biochemically Recurrent Prostate Carcinoma / PSA Failure / PSA Progression1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00829 mg/mLALOGPS
logP1.01ALOGPS
logP-3.2ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)0.85ChemAxon
pKa (Strongest Basic)9.5ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area381.39 Å2ChemAxon
Rotatable Bond Count35ChemAxon
Refractivity278.41 m3·mol-1ChemAxon
Polarizability96.08 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
Specific Function
Endopeptidase activity
Gene Name
KLK3
Uniprot ID
P07288
Uniprot Name
Prostate-specific antigen
Molecular Weight
28741.1 Da
References
  1. FDA Approved Drug Products: Gallium Ga 68 PSMA-11 Injection, for intravenous use [Link]

Drug created on December 13, 2020 23:28 / Updated on December 20, 2020 03:35