Development of a carbon-14 labeling approach to support disposition studies with a pegylated biologic.
نویسندگان
چکیده
Although it is widely accepted that one can extend the pharmacokinetic half-life of a therapeutic protein by covalent conjugation with polyethylene glycol (PEG), the disposition properties of such biologics have not yet been fully evaluated. Therefore, a novel [¹⁴C]-labeling method was developed that can be applied to a biologic conjugated with PEG through a maleimide-cysteine reaction. The method was used to study the tissue and tumor distribution of a PEGylated Adnectin, a recombinant protein derived from the 10th type III domain of fibronectin, in nude mice bearing human xenograft tumors. The PEGylated Adnectin contained a 40-kDa branched PEG (P40B) that was labeled with [¹⁴C] at the linker region between the PEG and Adnectin, without compromising cellular activity and plasma half-life in mice. After a single intravenous or intraperitoneal dose (33 mg/kg, 1.7 μCi per mouse) of [¹⁴C]-P40B-Adnectin, quantitative whole-body autoradiography analysis revealed that the liver had the highest uptake of the radioactivity among nontumor tissues, followed by the kidneys and lung. The muscle and brain showed the least penetration of the radioactivity among all tissues examined. In addition, the [¹⁴C]-P40B-EI-tandem penetrated into the tumor tissue, although the extent of accumulation was largely dependent on tumor type. Therefore, it was possible to assess the tissue distribution of a PEGylated biologic after it had been [¹⁴C] labeled using the novel method described herein.
منابع مشابه
DMD # 44792 1 Development of a Carbon - 14 Labeling Approach to Support Disposition Studies with a Pegylated Biologic
متن کامل
Plant sink-source relationships and carbon isotopic labeling techniques . Taher Barzegar* and Fatemhe Nekounam
The concept of source and sink strength is presently well-recognized and accepted by the scientific community as a pertinent approach describing the mechanisms of carbohydrate partitioning into the different and competing organs at a whole plant or canopy scales. Sink–source relationships have a clear role in the size of sink organs. Besides the effect on organ size, sink/source ratio might also...
متن کاملConvenient method for synthesis of a carbon-14 analogue of DL-Phenyl alanine
DL-Phenyl alanine labeled with carbon-14 in the α-position has been synthesized from ethyl[2-14C] acetate as part of a 6-step sequence.
متن کاملEvaluation of the Effect of PEGylated Single-Walled Carbon Nanotubes on Viability and Proliferation of Jurkat Cells
Among the numerous nanosized drug delivery systems currently under investigation, carbon nanotubes (CNTs), regardless of being single or multiple-walled, offer several advantages and are considered as promising candidates for drug targeting. Despite the valuable potentials of CNTs in drug delivery, their toxicity still remains an important issue. After the PEGylation of single-walled CNTs ...
متن کاملDevelopment of decision support tool for municipal solid waste management system in Iran based on life cycle assessment approach
Background and Objective: Various aspects including the environmental burdens, social and economic consequences of the waste management(WM) scenarios must be considered to come up with a comprehensive WM plan. Life Cycle Assessment (LCA) approach is a systematic method to quantify the environmental burdens of each WM scenario. Materials and Methods: This study used an LCA approach to develop a...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Drug metabolism and disposition: the biological fate of chemicals
دوره 40 9 شماره
صفحات -
تاریخ انتشار 2012