Synthesis and radioiodinationof tyramine cellobiose for labeling monoclonal antibodies

N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: Influence of isomeric substitution on radiolabeling and target cell residualization

“…To circumvent the loss of radioactivity from tumor cells after intracellular degradation of the radioiodinated mAbs [2, 3], a variety of residualizing labeling approaches have been developed including the use of iodotyramine-cellobiose conjugates [4-6], and d -amino acid peptide-DTPA conjugates [7], and peptides containing charged D-amino acids [8, 9]. …”

Synthesis of N-succinimidyl 4-guanidinomethyl-3-[*I]iodobenzoate: a radio-iodination agent for labeling internalizing proteins and peptides

“…With these methods, the portion of the molecule bearing the label is inert to lysosomal degradation and becomes trapped inside the cell after mAb proteolysis. The first set of reagents for this purpose (e.g., tyramine-cellobiose (TCB) and inulin-tyramine) contained a non-metabolizable carbohydrate moiety in their structure [10][11][12][13][14] . Use of these methods to label internalizing mAbs generally resulted in improved tumor retention of radioactivity compared with their directly iodinated counterparts.…”

“…Use of these methods to label internalizing mAbs generally resulted in improved tumor retention of radioactivity compared with their directly iodinated counterparts. However, there are a number of disadvantages associated with this labeling approach, including low protein-labeling yields, low immunoreactivity of the labeled mAbs, protein cross-linking and (as a result of the latter) higher liver uptake 10,[14][15][16] . A more successful method for radio-iodination of internalizing mAbs involves the use of oligopeptides composed of D-amino acids 3,17 .…”

l-Tyrosine Confers Residualizing Properties to ad-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies

“…32 In an attempt to trap radioiodinated catabolites in lysosomes, various strategies have been developed. [16][17][18][19][20][21][22][23][24][25][26][27][28] A DTPA-appended D-amino acid-containing peptide IMP-R4 was used before to label ch806 with 124 I and demonstrated targeting and biodistribution properties comparable to 111 In-CHX-A 00 -DTPA-ch806 in U87MG.de2-7 xenografts. 11 In this study, a D-amino acid-rich peptide for residualizing radioiodine labeling, PEG 4 -DThr-DPro-DThr-DAsp-DAsp-Tyr-DAsp-DAsp-DThr-DPro-DThr (PEG 4 -tptddYddtpt), was designed based on the known contribution of proline motifs and D-amino acids in resisting proteolytic degradation of peptides 29,33 and the observation that the use of a flanking D-amino acid motif DThr-DPro-DThr protects a central L-amino acid peptide sequence from proteolytic degradation.…”

“…14,15 When such antibodies are labeled directly with radiohalogens such as 124 I via endogenous tyrosine residues, resultant radiocatabolites diffuse out of the lysosomes, resulting in reduced overall uptake and retention in tumors. Various residualizing ligands for radioiodination, including nonmetabolizable carbohydrate-tyramine adducts, [16][17][18][19][20][21] aromatic acylation agents bearing substituents that will remain charged at lysosomal pH, [22][23][24] short D-amino acid peptides, 25,26 and DTPA-appended D-amino acid containing peptides, 27,28 have been developed with varying degrees of success and ease of use. These residualizing ligands resist lysosomal degradation and are trapped within the cell after antibody proteolysis.…”