Preparation, quality control and biodistribution studies of [67Ga]-DOTA-anti-CD20

Abstract

Rituximab / Gallium-67 / Radiolabeling / Quality control / DOTASummary. Rituximab was successively labeled with [ 67 Ga]-gallium chloride. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 • C using DOTA, N-hydroxy succinimide (NHS) in CH 2 Cl 2 . DOTA-Rituximab was obtained by the addition of 1 mL of a Rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH = 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 • C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 • C in 3 h. Radiothin layer chromatography showed an overall radiochemical purity of 90%-95% at optimized conditions (specific activity = 30 GBq/mg, labeling efficacy; 82%). The final isotonic 67 Ga-DOTA-rituximab complex was checked by gel electrophoresis for radiolysis. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 µm filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h.

Preparation and biological evaluation of [67Ga]-labeled-superparamagnetic nanoparticles in normal rats

“…Due to our recent works on the labeling and use of various biologically active molecules with cyclotron-derived radioisotopes [11,12], we were interested in radiolabeling of SPION samples for the visualization of the tracer alterations in nanoparticle attachment biologically and the possibility of the use of this alteration for targeting imaging/therapeutic radionuclides specifically to certain organs.…”

Development of 170Tm‐DOTA‐cetuximab for radioimmunotherapy

“…Because of the high boiling point of such solvents and the possibility of protein denaturing caused by these solvents, we tried to use dichloromethane on the basis of the previous reports for DCC‐mediated conjugation reactions. This reaction is performed at room temperature and can be done overnight as reported …”

“…This compound was prepared according to methods previously given in the literature with slight modifications . For a single run, a mixture of DOTA in acidic form (4.04 mg, 0.01 mmol), N ‐hydroxysuccinicimide (1.15 mg, 0.01 mmol), and dicyclohexyl carbodiimide (DCC) (2 mg, 0.01 mmol) were dissolved in anhydrous CH 2 Cl 2 (300–500 µl) under a blanket of N 2 in a glass vial.…”

Preparation and quality control of166Ho-DTPA-antiCD20 for radioimmunotherapy

“…It is already known that the cation 166 Ho 3+ has good chelating properties with polyaminopolycarboxylic acids, such as DTPA [10] and in continuation of our work on the development of radiolabeled rituximab radioimmunoconjugates for use in imaging and therapy of lymphomas [11,12], we have now focused on the development of Ho-166 based rituximab kit for ultimate radioimmunotherapy applications.…”