Improved radioiodination of 1,2-dipalmitoyl-3-IPPA via a tributyltin intermediate.

Abstract 1,2-Palmitoyl-3-[15-(4-iodophenyl)pentadecan-3-oyl]- rac -glyceroI (MIPAG) is a new agent for the clinical evaluation of pancreatic lipase activity and has demonstrated promise in preliminary clinical studies with patients affected with pancreatic insufficiency. Iodine-131-MIPAG was initially prepared via thallium-iodide displacement. Because of the need for a simple method which is amendable for the routine clinical use of MIPAG we have investigated the preparation and radioiodination of MIPAG utilizing the tributyltin precursor, 1,2-palmitoyl-3-[15-(-4-tributylstannylphenyl)pentadecan-3-oyl]- rac -glyceroI (TBT-MIPAG, 2 ). Compound 2 was prepared via the condensation of 1,2-palmitoyl- rac -glycerol with 15-(4-tributylstannylphenyl)pentadecanoic acid (TBT-PPA) prepared from 4-bromophenylacetylene. Electrophilic radioiodination using peracetic acid with sodium iodide-125 in ethanol at 80°C for 60 min afforded I-125-MIPAG in 65.9% (±11.5%) yield and radiochemical purity of 94% (±3.0%) after C-18 Sep-Pak purification ( n =6). This improved method for radioiodination utilizing TBT-MIPAG now provides radioiodinated MIPAG for routine clinical evaluation.