NDLI: Comparison of Succinimidyl [$^{125}$I]Iodobenzoate with Iodogen Iodination Methods to Study Pharmacokinetics and ADME of Biotherapeutics

Content Provider	Springer Nature Link
Author	Chen, Jianqing Wang, Mengmeng Joyce, Alison DeFranco, David Kavosi, Mania Xu, Xin O’Hara, Denise M.
Copyright Year	2014
Abstract	To assess the application of succinimidyl iodobenzoate (SIB) iodination method in labeling biotherapeutics to study their pharmacokinetics (PK) and biodistribution.An IgG molecule (protein-01) and a 40 KDa protein (protein-02) were evaluated. Pharmacokinetics (PK) and biodistribution of the radiolabeled IgG ($^{125}$I-protein-01) in mice compared parameters from SIB and Iodogen protein iodination labeling methods. In addition, PK of radiolabeled 40 KDa protein ($^{125}$I-protein-02) using SIB was compared with non-labeled protein-02 analyzed by ligand binding assay (LBA).Up to 72 h following a single IP injection to mice, the percentage of “free-label” determined by the soluble counts after TCA precipitation to total radioactivity in serum samples was 2.8–49.4% vs. <1.0% for $^{125}$I-protein-01 iodinated via Iodogen or SIB methods, respectively, suggesting a higher in vivo stability of $^{125}$I-protein-01 labeled via the SIB method. The serum exposure of $^{125}$I-protein-01 was two-fold higher, and correspondingly, the tissue exposure was also higher (averaging 3.6 fold at 168 h) when using SIB protein labeling method than when using the Iodogen method. In addition, following subcutaneous (SC) administration to mice, the serum exposure of $^{125}$I-protein-02 labeled via SIB method was similar to protein-02 measure by LBA.In this study, iodination of proteins using SIB methodology has overcome the dehalogenation problem in vivo which is inherent in Iodogen method, and PK parameters of a protein iodinated via SIB were comparable to the un-labeled protein measured by LBA. The SIB iodination method is an improved labeling approach for biotherapeutics used in studying PK and biodistribution characteristics.
Starting Page	2810
Ending Page	2821
Page Count	12
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	31
Issue Number	10
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2014-05-21
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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