Photoreactive 111In-cyclodextrin inclusion complex: a new heterobifunctional reagent for antibody labeling

Abstract

The compound of interest, N-5-azido-2-nitrobenzoylaminomethyl- 111In-acetylacetone-α-cyclodextrin (CD) ( V) was synthesized by the selective tosylation of α-CD to form 6-tosyl-6-deoxy-CD, which was then reacted with NaN 3 to form 6-azido-6-deoxy-CD ( II). This was followed by catalytic hydrogenation to yield III. Compound III and 111In-acetylacetone were mixed to form an inclusion complex, which was then reacted with N-5-azido-2-nitrobenzoyloxysuccinimide to yield compound V. Anti-melanoma MAbTP41.2 was added to compound V, followed by immediate photoreactivation labeling by u.v. light at 320 nm. The final product VI was purified from a Sephadex G-50 column. 111In-DTPA-MAbTP41.2 was also prepared as a control. Immunoreactivity via the cell-binding assay of VI was 87%, compared with 57% by the BADTPA method. Biodistribution in non-tumor rats yielded a liver concentration in %ID/g of 3.5, 1.7 and 1.0 for compound VI, compared to the 5.5, 5.2 and 3.1 for the BADTPA compound, at 4, 24 and 48 h post-injection, respectively.