title: Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results.
abstract: The present study describes the optimization of (68)Ga radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([(68)Ga]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the (68)Ga labeled product for imaging and treating angiogenesis respectively.
authors.affiliation: Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India.
authors.forename: Aanchal
authors.initials: A
authors.lastname: Ghai
authors.affiliation: Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India. Electronic address: drbsingh5144@yahoo.com.
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Panwar Hazari
authors.affiliation: Department of Radiation Oncology, Free Radical and Radiation Biology Program, The University of Iowa, 500 N Road, ML B180 FRRB, Iowa City, IA, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schultz
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, India.
authors.forename: Ambika
authors.initials: A
authors.lastname: Parmar
authors.affiliation: Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India.
authors.forename: Pardeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Centre for Nuclear Medicine, Punjab University, Chandigarh 160 014, India.
authors.forename: Devinder
authors.initials: D
authors.lastname: Dhawan
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi 110054, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar Mishra
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging; D050091:Dendrimers / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D050091:Dendrimers; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; C104700:PAMAM Starburst; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
keywords: Angiogenesis; DOTA-NHS; Gallium-68 complexes; Nanoparticles; PAMAM conjugates; Radiolabeling