Premium
SU‐E‐T‐325: Development of a Radioscandium Immunoconjugate for Radioimunotherapy
Author(s) -
Moghaddam L,
Jalilian A
Publication year - 2011
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.3612279
Subject(s) - dota , immunoconjugate , biodistribution , chemistry , radiochemistry , scandium , radioimmunotherapy , chromatography , vial , nuclear chemistry , nuclear medicine , chelation , monoclonal antibody , medicine , antibody , biochemistry , organic chemistry , immunology , in vitro
Purpose: Developing monoclonal antibodies with beta‐emitters has led to the introduction of important agents in radioimmunotherapy. In this work, Sc‐46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm‐2.s‐1) of natural metallic scandium sample followed by dissolution in acidic media (radiochemical purity ITLC, >99%) as a substitute for 47Sc in radiolabeling studies. Methods: 46Sc was produced with a specific activity of approximately 7.0–7.5 mCi/mg and radionuclidic purity of >98% by irradiation. NHS DOTA was freshly prepared and kept under a blanket of dry N2. Rituximab (MabThera) was used without further purification. Whatman No. 1 paper was obtained from Whatman (Maidstone, UK) for instant thin layer chromatography (ITLC). Radio‐chromatography was performed by using a bioscan AR‐2000 radio TLC scanner instrument (Bioscan). A high purity germanium (HPGe) detector coupled with a Canberra™ (model GC1020‐7500SL) multichannel analyzer and a dose calibrator ISOMED 1010 were used for counting distributed activity in rat organs. Results: The liver is the major target organ due to the presence of metaloproteins, apart from the liver, the spleen is the second major accumuation target.Thus, transferrin is principally responsible for scandium metabolism in vivo, while binding with ferritin is negligible []. Slight differences in the reported biodistribution data and the present work are possibly because of using rats instead of mice. Conclusions: As an immunoconjugate model, rituximab was conjugated with DOTA chelating agent, followed by 46Sc‐radiolabeling. The biodistributions of radiopharmaceutically acceptable 46ScCl3 and 46Sc‐DOTA‐rituximab formulations were checked in wild‐type rats up to 72 hours post injection. The biodistribution of 46ScCl3 among the tissues were in agreement with the former reports, while 46Sc‐DOTA‐rituximab accumulated mostly in the liver and spleen as shown in many other radiolabeled anti‐CD20 immunoconjugates. The development of other 47Sc‐labeled‐monoclonal antibodies for ultimate radioimmunotherapy based on this study using long‐half life, 46Sc radionuclide is possible.