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• W2045975003 abstract "We have devised and estimated a new strategy to prolong the residence time of radiolabeled antibodies in tumor in which an octaarginine peptide (R₈) was used as an anchoring molecule to fix antibodies against CD20 (NuB2; IgG2a) on tumor cells. Conjugation of R₈ with antibodies was performed by maleimide-thiol chemistry using thiol groups generated by reducing the disulfide bonds of the antibody. The R₈-conjugated NuB2 was then reacted with succinimidyl meta-[¹²⁵I]iodobenzoate to prepare [¹²⁵I]SIB-NuB2(I) (0.92 R₈/NuB2) and [¹²⁵I]SIB-NuB2(III) (3.38 R₈/NuB2). Both SIB-NuB2(I) and SIB-NuB2(III) exhibited size-exclusion HPLC elution profiles and immunoreactivity to CD20-positive cells similar to those of NuB2. NuB2(I) also possessed isoelectric focusing (IEF) profile similar to NuB2. However, NuB2(III) registered a broad IEF band toward higher pI. When incubated with CD20-positive cells, [¹²⁵I]SIB-NuB2(I) and [¹²⁵I]SIB-NuB2(III) exhibited 1.4 and 4.0 times higher cell-associated radioactivity than [¹²⁵I]SIB-NuB2. After the cells were washed and reincubated in a fresh medium for 3 h, [¹²⁵I]SIB-NuB2(I) and [¹²⁵I]SIB-NuB2(III) exhibited significantly higher cell-associated radioactivity than [¹²⁵I]SIB-NuB2. In biodistribution studies in normal mice, while both [¹²⁵I]SIB-NuB2(I) and [¹²⁵I]SIB-NuB2 exhibited similar biodistribution profiles, [¹²⁵I]SIB-NuB2(III) showed faster clearance from the blood and higher hepatic radioactivity levels than [¹²⁵I]SIB-NuB2. In SCID mice bearing CD20-positive xenografts, [¹³¹I]SIB-NuB2(I) exhibited significantly higher radioactivity in xenografts than those of [¹²⁵I]SIB-NuB2 with no significant increase being observed in other tissues. The findings indicate that appropriate R₈ modification of antibodies satisfies both specific targeting ability of antibody and strong cell-association property of R₈, which was reflected in the increased radioactivity levels in tumor. These findings supported the applicability of this approach to enhance target-specific accumulation of radiolabeled antibodies." @default.
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• W2045975003 date "2010-10-25" @default.
• W2045975003 modified "2023-09-24" @default.
• W2045975003 title "Enhanced Target-Specific Accumulation of Radiolabeled Antibodies by Conjugating Arginine-Rich Peptides as Anchoring Molecules" @default.
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• W2045975003 doi "https://doi.org/10.1021/bc100259q" @default.
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