title: Preclinical Comparative Study of (68)Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA.
abstract: (68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). (68)Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to (68)Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. (68)Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation (68)Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Ray Banerjee
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Ala
authors.initials: A
authors.lastname: Lisok
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D005710:Gallium Radioisotopes; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011849:Radioactive Tracers; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000954:Antigens, Surface; D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; C075313:N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D004492:Edetic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II