Home
Resources
Publications
Anti-mouse Monoclonal Antibody Immunoglobulin G Conjugated to GRKKRRQRRRPPQGYG-diethylenetriamine Pentaacetic Acid-[

Anti-mouse Monoclonal Antibody Immunoglobulin G Conjugated to GRKKRRQRRRPPQGYG-diethylenetriamine Pentaacetic Acid-[

Arvind Chopra

PMID: 20641335

Abstract:

Monoclonal antibodies (mAb) are often directed toward cell-surface molecules and may be radiolabeled for the imaging or treatment of cancer and other ailments (1-3). The radiolabeled mAbs are not readily internalized by the cell except by receptor-mediated endocytosis, which limits the use of these macromolecules either for the imaging or treatment of neoplastic solid tumors (4). However, Hu et al. showed that linking the mAb to the tat peptide (17 amino acid residues in the following sequence: GRKKRRQRRRPPQGYG) derived from the human immunodeficiency virus 1 (HIV-1) transactivator of the transcription (TAT) protein enabled it to be internalized and to be directed to the cellular nucleus (5, 6). Several investigators have used the tat peptide to enable cell penetration by a variety of large molecules including proteins, oligodeoxynucleotides, liposomes, and even nanoparticles (7-9). Conjugation of the tat peptide to mouse immunoglobulins (mIgG) labeled with radioactive iodine (123I) was shown to enhance cellular internalization of [123I]mIgG under in vitro conditions in human breast cancer MDA-MB-468 cells and also in xenograft tumors derived from these cells in athymic mice (6). The investigators used a similar approach to construct and direct p21WAF-1/Cip-1, another 123I-labeled mAb against the intranuclear cyclin-dependent kinase inhibitor; p21WAF-1/Cip-1 was preferentially retained in xenograft tumors in athymic mice injected intratumorally with epidermal growth factor to induce the expression of p21WAF-1/Cip-1 (5). However, radiostability of the tat peptide (i.e., 123I-labeled mAb) is a major limitation of its use to target the intracellular or intranuclear epitopes because loss of the radiolabel can lead to the delivery of a suboptimal radioactivity dose to the cancerous lesions; in addition, 123I has a short half-life (13.3 h), so it is not possible to perform imaging studies for prolonged periods, especially when the tumor/background ratios are usually highest at 72 h after the administration of a radiolabeled mAb (10).
Press et al. showed that mAbs labeled with radioactive indium (111In; half-life = 2.8 days) and conjugated to the tat peptide were more stable in vivo compared with those labeled with 123I; 111In-labeled mAbs generate a higher tumor/background ratio, including internalization into the nucleus of human breast cancer BT-474 cells (11). In addition, the 111In-labeled and tat peptide-conjugated, anti-mIgG ([111In]anti-mIgG-tat) were retained two times longer by the cells compared to the same tat peptide-linked mAb labeled with 123I (11). In an effort to extend this work, Cornelissen et al. investigated the biodistribution and nuclear importation of [111In]anti-mIgG-tat in normal tissue and BT-474 cell xenograft tumors in athymic mice (4). These studies are briefly described in this chapter.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412620	Anti-Cdc7 Kinase antibody, Mouse monoclonal			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: