Preparation of clinical-scale177Lu-Rituximab: Optimization of protocols for conjugation, radiolabeling, and freeze-dried kit formulation.
Rituximab is a monoclonal chimeric antibody, which has been approved by the US Food and Drug Administration for immunotherapy of non-Hodgkin lymphoma. Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of non-Hodgkin lymphoma; however, they are of murine origin that reduces their treatment efficacy. So as to circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (bifunctional chelating agent and antibody) and radiolabeling procedures for the preparation of clinical-scale177Lu-labeled Rituximab. An attempt was also made to prepare the freeze-dried Rituximab kit for the easy and convenient clinical translation of the agent. Clinical-scale177Lu-Rituximab (40 mCi, 1.48 GBq) was prepared with >95% radiochemical purity using the kit. Biological evaluation of177Lu-Rituximab was performed by in vitro cell binding studies in Raji cell lines, which showed satisfactory binding at 4°C and 37°C. Pharmacokinetic behavior of the agent, evaluated by biodistribution studies in normal Swiss mice, revealed high blood and liver uptake at the initial time points, although it exhibited slow and gradual clearance with time. The study indicates that clinical-scale177Lu-Rituximab could be conveniently formulated using the methodology described in the present article.
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
Mohini
M
Guleria
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.|Homi Bhabha National Institute, Mumbai, India.
Tapas
0000-0003-2877-0683
T
Das
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
Chandan
C
Kumar
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
Jeyachitra
J
Amirdhanayagam
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
Haladhar D
HD
Sarma
Homi Bhabha National Institute, Mumbai, India.|Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India.
Sharmila
S
Banerjee
D000818:Animals; D045744:Cell Line, Tumor; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005612:Freeze Drying; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008187:Lutetium / Q000737:chemistry*; D051379:Mice; D011868:Radioisotopes; D000069283:Rituximab / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000069283:Rituximab; D008187:Lutetium
177Lu; 177Lu-Rituximab; Rituximab; freeze-dried Rituximab kit; radioimmunotherapy