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

• 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.
• [68Ga] DOTA–PAMAM-Dhas rapid blood clearance and excreted mainly through the kidneys.
• No significant retention of the radiotracer was seen in any other organ.

The present study describes the optimization of 68Ga 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 ([68Ga]-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 αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the 68Ga labeled product for imaging and treating angiogenesis respectively.

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