Radiolabeling optimization and characterization of 68Ga labeled DOTA–polyamido-amine dendrimer conjugate – Animal biodistribution and PET imaging results. (November 2015)

• Record Type: Journal Article
• Authors: Ghai, Aanchal; Singh, Baljinder; Panwar Hazari, Puja; Schultz, Michael K.; Parmar, Ambika; Kumar, Pardeep; Sharma, Sarika; Dhawan, Devinder; Kumar Mishra, Anil
• Is Part Of: Applied radiation and isotopes. Volume 105(2015:Nov.)
• Page Start: 40
• Page End: 46
• Publication Date: 2015-11
• Subjects: Gallium-68 complexes -- PAMAM conjugates -- DOTA-NHS -- Radiolabeling -- Nanoparticles -- Angiogenesis; Radiology -- Periodicals; Radiation -- Industrial applications -- Periodicals; Nuclear chemistry -- Periodicals; Internet resource; Periodical; 660.298
• DOI: 10.1016/j.apradiso.2015.07.021
• Languages: English
• ISSNs: 0969-8043

Abstract

Abstract: The present study describes the optimization of 68 Ga radiolabeling with PAMAM dendrimer–DOTA conjugate. A conjugate (PAMAM–DOTA) concentration of 11.69 µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0 min 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 1.0 h. 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 1 h 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 αV β3 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. Graphical abstract: Highlights: Chemical conjugation of G-4 PAMAM dendrimers with DOTA-NHS carried out successfully. Purification and characterization of the conjugate was done by SEC and MALDI-TOF. Radiolabeling of PAMAM-DOTA-conjugate with 68Ga yielded high radiolabeling efficiency. [ 68 Ga] DOTA–PAMAM-Dhas rapid blood clearance and excreted mainly through the kidneys. No significant retention of the radiotracer was seen in any other organ.