title: Integrin αvβ3 as a Promising Target to Image Neoangiogenesis Using In-House Generator-Produced Positron Emitter (68)Ga-Labeled DOTA-Arginine-Glycine-Aspartic Acid (RGD) Ligand.
abstract: For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors.
authors.affiliation: 1 Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India .
authors.forename: Rakhee
authors.initials: R
authors.lastname: Vatsa
authors.affiliation: 2 Centre for Nuclear Medicine, Punjab University , Chandigarh, India .
authors.forename: Priya
authors.initials: P
authors.lastname: Bhusari
authors.affiliation: 1 Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India .
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: 3 Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: 3 Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
authors.affiliation: 4 Department of Surgery, PGIMER, Chandigarh, India .
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Singh
authors.affiliation: 2 Centre for Nuclear Medicine, Punjab University , Chandigarh, India .
authors.forename: Devinder Kumar
authors.initials: DK
authors.lastname: Dhawan
authors.affiliation: 1 Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India .
authors.forename: Jaya
authors.initials: J
authors.lastname: Shukla
authors.affiliation: 1 Department of Nuclear Medicine and PET, PGIMER, Chandigarh, India .
authors.forename: Bhagwant Rai
authors.initials: BR
authors.lastname: Mittal
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000000981:diagnostic imaging*; D005260:Female; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008875:Middle Aged; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
chemical_list: C000605805:68Ga-DOTA-Arg-Gly-Asp; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals
keywords: 68Ga; PET/CT imaging; RGD; angiogenesis; αvβ3 integrin